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Differences of Sex Development v1.6 DMRT1 Zornitza Stark Publications for gene: DMRT1 were set to PMID: 31479588; 24934491; 29527098
Differences of Sex Development v1.5 DMRT1 Zornitza Stark Phenotypes for gene: DMRT1 were changed from Azoospermia to 46,XY disorder of sex development, MONDO:0020040
Differences of Sex Development v1.4 DMRT1 Zornitza Stark Classified gene: DMRT1 as Amber List (moderate evidence)
Differences of Sex Development v1.4 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v1.3 NR0B1 Zornitza Stark Publications for gene: NR0B1 were set to 7951319
Differences of Sex Development v1.2 NR0B1 Tashunka Taylor-Miller reviewed gene: NR0B1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 28295047; Phenotypes: http://purl.obolibrary.org/obo/MONDO_0020040; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v1.2 DMRT1 Tashunka Taylor-Miller reviewed gene: DMRT1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 26005864, 28295047; Phenotypes: http://purl.obolibrary.org/obo/MONDO_0020040; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v1.2 UBR5 Bryony Thompson Marked gene: UBR5 as ready
Differences of Sex Development v1.2 UBR5 Bryony Thompson Gene: ubr5 has been classified as Green List (High Evidence).
Differences of Sex Development v1.2 UBR5 Bryony Thompson Classified gene: UBR5 as Green List (high evidence)
Differences of Sex Development v1.2 UBR5 Bryony Thompson Gene: ubr5 has been classified as Green List (High Evidence).
Differences of Sex Development v1.1 UBR5 Bryony Thompson gene: UBR5 was added
gene: UBR5 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: UBR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBR5 were set to 39721588
Phenotypes for gene: UBR5 were set to Neurodevelopmental disorder MONDO:0700092, UBR5-related
Review for gene: UBR5 was set to GREEN
Added comment: 29 individuals with a neurodevelopment syndrome (24 de novo variants) with a core phenotype characterised by developmental delay (26/28), autism (16/26), and intellectual disability (56%). Additionally, some individuals presented with epilepsy/seizures (11/27), movement disorders, and/or genital anomalies (35%). Loss of function is the expected mechanism of disease with functional experiments in C. elegans and in vitro ubiquitination assays.
Sources: Literature
Differences of Sex Development v1.0 Zornitza Stark promoted panel to version 1.0
Differences of Sex Development v0.380 TWNK Zornitza Stark Marked gene: TWNK as ready
Differences of Sex Development v0.380 TWNK Zornitza Stark Gene: twnk has been classified as Green List (High Evidence).
Differences of Sex Development v0.380 TWNK Zornitza Stark Phenotypes for gene: TWNK were changed from Perrault syndrome 5; MIM# 616138 to Perrault syndrome 5, MIM# 616138
Differences of Sex Development v0.379 TWNK Zornitza Stark Publications for gene: TWNK were set to PMID: 25355836, 31852434, 31455392
Differences of Sex Development v0.378 POLR1C Zornitza Stark Marked gene: POLR1C as ready
Differences of Sex Development v0.378 POLR1C Zornitza Stark Gene: polr1c has been classified as Red List (Low Evidence).
Differences of Sex Development v0.378 POLR1C Zornitza Stark Publications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949, ............22855961
Differences of Sex Development v0.375 AXL Zornitza Stark Marked gene: AXL as ready
Differences of Sex Development v0.375 AXL Zornitza Stark Gene: axl has been classified as Red List (Low Evidence).
Differences of Sex Development v0.375 SOX2 Zornitza Stark Marked gene: SOX2 as ready
Differences of Sex Development v0.375 SOX2 Zornitza Stark Gene: sox2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.375 POLR3B Zornitza Stark Marked gene: POLR3B as ready
Differences of Sex Development v0.375 POLR3B Zornitza Stark Gene: polr3b has been classified as Green List (High Evidence).
Differences of Sex Development v0.375 POLR3B Zornitza Stark Publications for gene: POLR3B were set to PubMed: 27512013, 23355746, 22036171, 22036172, 25339210, 33005949, 22855961
Differences of Sex Development v0.374 POLR3A Zornitza Stark Marked gene: POLR3A as ready
Differences of Sex Development v0.374 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Differences of Sex Development v0.374 POLR3A Zornitza Stark Publications for gene: POLR3A were set to PubMed: 21855841, 25339210, 33005949, 22855961
Differences of Sex Development v0.373 MARS2 Zornitza Stark Marked gene: MARS2 as ready
Differences of Sex Development v0.373 MARS2 Zornitza Stark Gene: mars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.373 MARS2 Zornitza Stark Publications for gene: MARS2 were set to PMID: 27650058, 21464306, 27087618
Differences of Sex Development v0.372 LARS2 Zornitza Stark Marked gene: LARS2 as ready
Differences of Sex Development v0.372 LARS2 Zornitza Stark Gene: lars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.372 LARS2 Zornitza Stark Phenotypes for gene: LARS2 were changed from Perrault syndrome 4; MIM# 615300 to Perrault syndrome 4, MIM# 615300
Differences of Sex Development v0.371 LARS2 Zornitza Stark Publications for gene: LARS2 were set to PMID: 32423379, 29205794, 23541342, 30737337, 26657938,
Differences of Sex Development v0.370 IRF6 Zornitza Stark Marked gene: IRF6 as ready
Differences of Sex Development v0.370 IRF6 Zornitza Stark Gene: irf6 has been classified as Green List (High Evidence).
Differences of Sex Development v0.370 HHAT Zornitza Stark Marked gene: HHAT as ready
Differences of Sex Development v0.370 HHAT Zornitza Stark Gene: hhat has been classified as Green List (High Evidence).
Differences of Sex Development v0.370 HHAT Zornitza Stark Publications for gene: HHAT were set to PMID: 24784881, 33749989, 35045414
Differences of Sex Development v0.369 HARS2 Zornitza Stark Marked gene: HARS2 as ready
Differences of Sex Development v0.369 HARS2 Zornitza Stark Gene: hars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.369 HARS2 Zornitza Stark Publications for gene: HARS2 were set to PMID: 27650058, 21464306, 27087618
Differences of Sex Development v0.368 FREM2 Zornitza Stark Marked gene: FREM2 as ready
Differences of Sex Development v0.368 FREM2 Zornitza Stark Gene: frem2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.368 FREM2 Zornitza Stark Publications for gene: FREM2 were set to PMID: 15838507, 29688405, 18203166, 18671281, 18000968
Differences of Sex Development v0.367 WT1 Zornitza Stark Marked gene: WT1 as ready
Differences of Sex Development v0.367 WT1 Zornitza Stark Gene: wt1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.367 WT1 Zornitza Stark Phenotypes for gene: WT1 were changed from to Wilms tumor, MONDO:0006058; Wilms tumor 1, MONDO:0008679; Wilms tumor, type 1, MIM#194070; Denys-Drash syndrome, MIM#194080; Frasier syndrome, MIM#136680
Differences of Sex Development v0.366 WT1 Zornitza Stark Mode of inheritance for gene: WT1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.365 SRY Zornitza Stark Marked gene: SRY as ready
Differences of Sex Development v0.365 SRY Zornitza Stark Gene: sry has been classified as Green List (High Evidence).
Differences of Sex Development v0.365 SRY Zornitza Stark Phenotypes for gene: SRY were changed from to 46XX sex reversal 1, MIM# 400045; 46XY sex reversal 1 , MIM#400044
Differences of Sex Development v0.364 SRY Zornitza Stark Publications for gene: SRY were set to
Differences of Sex Development v0.363 SRY Zornitza Stark Mode of inheritance for gene: SRY was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.362 SOX9 Zornitza Stark Marked gene: SOX9 as ready
Differences of Sex Development v0.362 SOX9 Zornitza Stark Gene: sox9 has been classified as Green List (High Evidence).
Differences of Sex Development v0.362 SOX9 Zornitza Stark Phenotypes for gene: SOX9 were changed from to Campomelic dysplasia, MIM# 114290; Campomelic dysplasia, MONDO:0007251; Acampomelic campomelic dysplasia, MIM # 114290, 46XX sex reversal 2, MIM# 278850; 46XY sex reversal 10, MIM # 616425
Differences of Sex Development v0.361 SOX9 Zornitza Stark Mode of inheritance for gene: SOX9 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.360 FGFR1 Zornitza Stark Marked gene: FGFR1 as ready
Differences of Sex Development v0.360 FGFR1 Zornitza Stark Gene: fgfr1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.360 FGFR1 Zornitza Stark Phenotypes for gene: FGFR1 were changed from to Encephalocraniocutaneous lipomatosis, somatic mosaic 613001; Hartsfield syndrome 615465; Hypogonadotropic hypogonadism 2 with or without anosmia 147950; Osteoglophonic dysplasia 166250
Differences of Sex Development v0.359 FGFR1 Zornitza Stark Publications for gene: FGFR1 were set to
Differences of Sex Development v0.358 FGFR1 Zornitza Stark Mode of inheritance for gene: FGFR1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.357 FGFR2 Zornitza Stark Marked gene: FGFR2 as ready
Differences of Sex Development v0.357 FGFR2 Zornitza Stark Gene: fgfr2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.357 FGFR2 Zornitza Stark Phenotypes for gene: FGFR2 were changed from to Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis,MIM# 207410, Apert syndrome, MIM# 101200, Beare-Stevenson cutis gyrata syndrome, MIM# 123790, Bent bone dysplasia syndrome, MIM# 614592
Differences of Sex Development v0.356 FGFR2 Zornitza Stark Publications for gene: FGFR2 were set to
Differences of Sex Development v0.355 FGFR2 Zornitza Stark Mode of inheritance for gene: FGFR2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.354 FSHB Zornitza Stark Marked gene: FSHB as ready
Differences of Sex Development v0.354 FSHB Zornitza Stark Gene: fshb has been classified as Green List (High Evidence).
Differences of Sex Development v0.354 FSHB Zornitza Stark Phenotypes for gene: FSHB were changed from to Hypogonadotropic hypogonadism 24 without anosmia, MIM#229070
Differences of Sex Development v0.353 FSHB Zornitza Stark Publications for gene: FSHB were set to
Differences of Sex Development v0.352 FSHB Zornitza Stark Mode of inheritance for gene: FSHB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.351 FSHR Zornitza Stark Phenotypes for gene: FSHR were changed from to Ovarian dysgenesis 1 MONDO:0024463; Ovarian hyperstimulation syndrome MONDO:0011972
Differences of Sex Development v0.350 FSHR Zornitza Stark Marked gene: FSHR as ready
Differences of Sex Development v0.350 FSHR Zornitza Stark Gene: fshr has been classified as Green List (High Evidence).
Differences of Sex Development v0.350 FSHR Zornitza Stark Publications for gene: FSHR were set to
Differences of Sex Development v0.349 FSHR Zornitza Stark Mode of inheritance for gene: FSHR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.348 FSHR Chirag Patel reviewed gene: FSHR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16630814, 7553856, 9020851, 9769327, 20087398, 9854118, 12930928, 12930927, 17721928, 26911863; Phenotypes: Ovarian dysgenesis 1 MONDO:0024463, Ovarian hyperstimulation syndrome MONDO:0011972; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.348 FSHB Chirag Patel reviewed gene: FSHB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 8220432, 9280841, 9624193, 9806482, 9271483, 16630814; Phenotypes: Hypogonadotropic hypogonadism 24 without anosmia, MIM#229070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.348 FGFR2 Chirag Patel reviewed gene: FGFR2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29848297, 32879300; Phenotypes: Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis,MIM# 207410, Apert syndrome, MIM# 101200, Beare-Stevenson cutis gyrata syndrome, MIM# 123790, Bent bone dysplasia syndrome, MIM# 614592; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.348 FGFR1 Chirag Patel reviewed gene: FGFR1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18034870, 23812909, 26942290; Phenotypes: Encephalocraniocutaneous lipomatosis, somatic mosaic 613001, Hartsfield syndrome 615465, Hypogonadotropic hypogonadism 2 with or without anosmia 147950, Osteoglophonic dysplasia 166250; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.348 SOX9 Chirag Patel reviewed gene: SOX9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Campomelic dysplasia, MIM# 114290, Campomelic dysplasia, MONDO:0007251, Acampomelic campomelic dysplasia, MIM # 114290, 46XX sex reversal 2, MIM# 278850, 46XY sex reversal 10, MIM # 616425; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.348 SRY Chirag Patel reviewed gene: SRY: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 9143916 15863672; Phenotypes: 46XX sex reversal 1, MIM# 400045, 46XY sex reversal 1 , MIM#400044; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.348 WT1 Chirag Patel reviewed gene: WT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Wilms tumor, MONDO:0006058, Wilms tumor 1, MONDO:0008679, Wilms tumor, type 1, MIM#194070, Denys-Drash syndrome, MIM#194080, Frasier syndrome, MIM#136680; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.348 FRAS1 Zornitza Stark Marked gene: FRAS1 as ready
Differences of Sex Development v0.348 FRAS1 Zornitza Stark Gene: fras1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.348 FRAS1 Zornitza Stark Publications for gene: FRAS1 were set to PMID: 12766769, 18671281, 18000968
Differences of Sex Development v0.347 FGF8 Zornitza Stark Marked gene: FGF8 as ready
Differences of Sex Development v0.347 FGF8 Zornitza Stark Gene: fgf8 has been classified as Green List (High Evidence).
Differences of Sex Development v0.347 FGF8 Zornitza Stark Phenotypes for gene: FGF8 were changed from to Hypogonadotropic hypogonadism 6 with or without anosmia, MIM# 612702
Differences of Sex Development v0.346 FGF8 Zornitza Stark Publications for gene: FGF8 were set to
Differences of Sex Development v0.345 FGF8 Zornitza Stark Mode of inheritance for gene: FGF8 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.344 FGF8 Zornitza Stark reviewed gene: FGF8: Rating: GREEN; Mode of pathogenicity: None; Publications: 20463092, 18596921, 24280688, 31748124; Phenotypes: Hypogonadotropic hypogonadism 6 with or without anosmia, MIM# 612702; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.344 DHCR7 Zornitza Stark Marked gene: DHCR7 as ready
Differences of Sex Development v0.344 DHCR7 Zornitza Stark Gene: dhcr7 has been classified as Green List (High Evidence).
Differences of Sex Development v0.344 DHCR7 Zornitza Stark Phenotypes for gene: DHCR7 were changed from to Smith-Lemli-Opitz syndrome, MIM#270400
Differences of Sex Development v0.343 DHCR7 Zornitza Stark Mode of inheritance for gene: DHCR7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.342 DHCR7 Zornitza Stark reviewed gene: DHCR7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Smith-Lemli-Opitz syndrome, MIM#270400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.342 CTU2 Zornitza Stark Marked gene: CTU2 as ready
Differences of Sex Development v0.342 CTU2 Zornitza Stark Gene: ctu2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.342 CTU2 Zornitza Stark Publications for gene: CTU2 were set to PMID: 27480277, 26633546, 31301155, 38348206
Differences of Sex Development v0.341 CHD7 Zornitza Stark Marked gene: CHD7 as ready
Differences of Sex Development v0.341 CHD7 Zornitza Stark Gene: chd7 has been classified as Green List (High Evidence).
Differences of Sex Development v0.341 CHD7 Zornitza Stark Phenotypes for gene: CHD7 were changed from to Hypogonadotropic hypogonadism 5 with or without anosmia MIM#612370; CHARGE syndrome MIM#214800
Differences of Sex Development v0.340 CHD7 Zornitza Stark Publications for gene: CHD7 were set to
Differences of Sex Development v0.339 CHD7 Zornitza Stark Mode of inheritance for gene: CHD7 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.338 CHD7 Zornitza Stark reviewed gene: CHD7: Rating: GREEN; Mode of pathogenicity: None; Publications: 26411921; Phenotypes: Hypogonadotropic hypogonadism 5 with or without anosmia MIM#612370, CHARGE syndrome MIM#214800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.338 CHD4 Zornitza Stark Marked gene: CHD4 as ready
Differences of Sex Development v0.338 CHD4 Zornitza Stark Gene: chd4 has been classified as Green List (High Evidence).
Differences of Sex Development v0.338 CHD4 Zornitza Stark Publications for gene: CHD4 were set to PMID: 31388190, 32881470
Differences of Sex Development v0.337 ATRX Zornitza Stark Marked gene: ATRX as ready
Differences of Sex Development v0.337 ATRX Zornitza Stark Gene: atrx has been classified as Green List (High Evidence).
Differences of Sex Development v0.337 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from to ATR-X-related syndrome MONDO:0016980
Differences of Sex Development v0.336 ATRX Zornitza Stark Mode of inheritance for gene: ATRX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.335 ATRX Zornitza Stark reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ATR-X-related syndrome MONDO:0016980; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.335 ARX Zornitza Stark Marked gene: ARX as ready
Differences of Sex Development v0.335 ARX Zornitza Stark Gene: arx has been classified as Green List (High Evidence).
Differences of Sex Development v0.335 ARX Zornitza Stark Phenotypes for gene: ARX were changed from to X-linked lissencephaly with abnormal genitalia, MONDO:0010268
Differences of Sex Development v0.334 ARX Zornitza Stark Publications for gene: ARX were set to
Differences of Sex Development v0.333 ARX Zornitza Stark Mode of inheritance for gene: ARX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.332 ARX Zornitza Stark reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: 14722918; Phenotypes: X-linked lissencephaly with abnormal genitalia, MONDO:0010268; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Differences of Sex Development v0.332 AR Zornitza Stark Marked gene: AR as ready
Differences of Sex Development v0.332 AR Zornitza Stark Gene: ar has been classified as Green List (High Evidence).
Differences of Sex Development v0.332 AR Zornitza Stark Phenotypes for gene: AR were changed from to Hypospadias 1, X-linked MIM#30063; Androgen insensitivity MIM#300068; Androgen insensitivity, partial, with or without breast cancer MIM#312300
Differences of Sex Development v0.331 AR Zornitza Stark Publications for gene: AR were set to
Differences of Sex Development v0.330 AR Zornitza Stark Mode of inheritance for gene: AR was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.329 AR Zornitza Stark reviewed gene: AR: Rating: GREEN; Mode of pathogenicity: None; Publications: 22334387; Phenotypes: Hypospadias 1, X-linked MIM#30063, Androgen insensitivity MIM#300068, Androgen insensitivity, partial, with or without breast cancer MIM#312300; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.329 AMHR2 Zornitza Stark Marked gene: AMHR2 as ready
Differences of Sex Development v0.329 AMHR2 Zornitza Stark Gene: amhr2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.329 AMHR2 Zornitza Stark Phenotypes for gene: AMHR2 were changed from to Persistent Mullerian duct syndrome, type II MIM#261550
Differences of Sex Development v0.328 AMHR2 Zornitza Stark Publications for gene: AMHR2 were set to
Differences of Sex Development v0.327 AMHR2 Zornitza Stark Mode of inheritance for gene: AMHR2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.326 AMHR2 Zornitza Stark reviewed gene: AMHR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34810374; Phenotypes: Persistent Mullerian duct syndrome, type II MIM#261550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.325 Chirag Patel Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Royal Melbourne Hospital; Rare Disease
Differences of Sex Development v0.324 FREM2 Chirag Patel Classified gene: FREM2 as Green List (high evidence)
Differences of Sex Development v0.324 FREM2 Chirag Patel Gene: frem2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.324 FREM2 Chirag Patel Classified gene: FREM2 as Green List (high evidence)
Differences of Sex Development v0.324 FREM2 Chirag Patel Gene: frem2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.323 FREM2 Chirag Patel Classified gene: FREM2 as Green List (high evidence)
Differences of Sex Development v0.323 FREM2 Chirag Patel Gene: frem2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.323 FRAS1 Chirag Patel Classified gene: FRAS1 as Green List (high evidence)
Differences of Sex Development v0.323 FRAS1 Chirag Patel Gene: fras1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.322 FRAS1 Chirag Patel gene: FRAS1 was added
gene: FRAS1 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: FRAS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRAS1 were set to PMID: 12766769, 18671281, 18000968
Phenotypes for gene: FRAS1 were set to Fraser syndrome 1, MIM#219000
Review for gene: FRAS1 was set to GREEN
Added comment: Fraser syndrome is an autosomal recessive malformation disorder. Major criteria include syndactyly, cryptophthalmos spectrum, urinary tract abnormalities, ambiguous genitalia, laryngeal and tracheal anomalies, and positive family history. Minor criteria include anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies.
Established gene-disease association.
Sources: Literature
Differences of Sex Development v0.321 FREM2 Chirag Patel gene: FREM2 was added
gene: FREM2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: FREM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FREM2 were set to PMID: 15838507, 29688405, 18203166, 18671281, 18000968
Phenotypes for gene: FREM2 were set to Fraser syndrome 2, MIM#617666
Review for gene: FREM2 was set to GREEN
Added comment: Fraser syndrome is an autosomal recessive malformation disorder. Major criteria include syndactyly, cryptophthalmos spectrum, urinary tract abnormalities, ambiguous genitalia, laryngeal and tracheal anomalies, and positive family history. Minor criteria include anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies.
Established gene-disease association.
Sources: Literature
Differences of Sex Development v0.320 SOX2 Chirag Patel Classified gene: SOX2 as Green List (high evidence)
Differences of Sex Development v0.320 SOX2 Chirag Patel Gene: sox2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.319 SOX2 Chirag Patel gene: SOX2 was added
gene: SOX2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: SOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX2 were set to PMID: 20301477
Phenotypes for gene: SOX2 were set to Anophthalmia/microphthalmia-esophageal atresia syndrome MONDO:0008799; Microphthalmia, syndromic 3, MIM# 206900; Optic nerve hypoplasia and abnormalities of the central nervous system, MIM# 206900
Review for gene: SOX2 was set to GREEN
Added comment: SOX2 disorder includes anophthalmia and/or microphthalmia, brain malformations, developmental delay / intellectual disability, oesophageal atresia, pituitary hypoplasia, postnatal growth delay, hypotonia, seizures, and spastic or dystonic movements, and hypogonadotropic hypogonadism (manifest as cryptorchidism and micropenis in males, gonadal dysgenesis infrequently in females, and delayed puberty in both sexes). Established gene-disease association.
Sources: Literature
Differences of Sex Development v0.318 IRF6 Chirag Patel Classified gene: IRF6 as Green List (high evidence)
Differences of Sex Development v0.318 IRF6 Chirag Patel Gene: irf6 has been classified as Green List (High Evidence).
Differences of Sex Development v0.317 IRF6 Chirag Patel gene: IRF6 was added
gene: IRF6 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: IRF6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF6 were set to PMID: 20301581
Phenotypes for gene: IRF6 were set to Popliteal pterygium syndrome 1, OMIM #119500
Review for gene: IRF6 was set to GREEN
Added comment: IRF6-related disorders span a spectrum from isolated cleft lip and palate and Van der Woude syndrome (VWS) at the mild end to popliteal pterygium syndrome (PPS) at the more severe end.
Established gene-disease association.

Popliteal pterygium syndrome (PPS) features including orofacial anomalies such as lower lip pits, cleft lip and/or palate, and syngnathia, and skin and genital abnormalities including webbing of the lower limbs, syndactyly, hypoplasia of the labia majora/vagina/uterus, cryptorchidism, and bifid or hypoplastic scrotum.
Sources: Literature
Differences of Sex Development v0.316 CHD4 Chirag Patel Classified gene: CHD4 as Green List (high evidence)
Differences of Sex Development v0.316 CHD4 Chirag Patel Gene: chd4 has been classified as Green List (High Evidence).
Differences of Sex Development v0.315 CHD4 Chirag Patel gene: CHD4 was added
gene: CHD4 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: CHD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD4 were set to PMID: 31388190, 32881470
Phenotypes for gene: CHD4 were set to Sifrim-Hitz-Weiss syndrome, MIM #617159
Review for gene: CHD4 was set to GREEN
Added comment: Sifrim-Hitz-Weiss syndrome is an autosomal dominant intellectual developmental disorder with variable congenital defects affecting other systems, including cardiac, skeletal, and urogenital. Some patients may have short stature, enlarged head circumference, hearing loss, and nonspecific dysmorphic facial features. Established gene-disease association.

Hypogonadism is common in males (cryptorchidism and/or microphallus), with hormonal profile consistent with hypogonadotropic hypogonadism.
Sources: Literature
Differences of Sex Development v0.314 POLR1C Chirag Patel gene: POLR1C was added
gene: POLR1C was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949
Phenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, OMIM#616494
Review for gene: POLR1C was set to RED
Added comment: Hypomyelinating leukodystrophy-11 (HLD11) is an autosomal recessive neurologic disorder characterized by delayed psychomotor development and other neurologic features associated with hypomyelination on brain imaging. Some patients may have additional nonneurologic features, particularly dental abnormalities and possibly hypogonadotropic hypogonadism.

Thiffault et al. (2015) reported 8 unrelated patients with hypomyelinating leukodystrophy and 13 homozygous or compound heterozygous mutations in the POLR1C gene. All had neurologic abnormalities, including delayed psychomotor development, loss or lack of independent ambulation, abnormal cognition, tremor, ataxia, spasticity, and cerebellar findings. Three had myopia and 3 had dental abnormalities. Six patients were too young to be assessed for hypogonadotropic hypogonadism, and 2 did not have hypogonadism.

Gauquelin et al. (2019) reported 23 patients with hypomyelinating leukodystrophy and 29 different variants (homozygous or compound heterozygous) in the POLR1C gene. Patients too young to comment on hypogonadotropic hypogonadism.
Sources: Literature
Differences of Sex Development v0.314 POLR1C Chirag Patel gene: POLR1C was added
gene: POLR1C was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949
Phenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, OMIM#616494
Review for gene: POLR1C was set to RED
Added comment: Hypomyelinating leukodystrophy-11 (HLD11) is an autosomal recessive neurologic disorder characterized by delayed psychomotor development and other neurologic features associated with hypomyelination on brain imaging. Some patients may have additional nonneurologic features, particularly dental abnormalities and possibly hypogonadotropic hypogonadism.

Thiffault et al. (2015) reported 8 unrelated patients with hypomyelinating leukodystrophy and 13 homozygous or compound heterozygous mutations in the POLR1C gene. All had neurologic abnormalities, including delayed psychomotor development, loss or lack of independent ambulation, abnormal cognition, tremor, ataxia, spasticity, and cerebellar findings. Three had myopia and 3 had dental abnormalities. Six patients were too young to be assessed for hypogonadotropic hypogonadism, and 2 did not have hypogonadism.

Gauquelin et al. (2019) reported 23 patients with hypomyelinating leukodystrophy and 29 different variants (homozygous or compound heterozygous) in the POLR1C gene. Patients too young to comment on hypogonadotropic hypogonadism.
Sources: Literature
Differences of Sex Development v0.314 POLR1C Chirag Patel gene: POLR1C was added
gene: POLR1C was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR1C were set to PMID: 26151409, 32042905, 33005949, ............22855961
Phenotypes for gene: POLR1C were set to Leukodystrophy, hypomyelinating, 11, OMIM#616494
Review for gene: POLR1C was set to RED
Added comment: Hypomyelinating leukodystrophy-11 (HLD11) is an autosomal recessive neurologic disorder characterized by delayed psychomotor development and other neurologic features associated with hypomyelination on brain imaging. Some patients may have additional nonneurologic features, particularly dental abnormalities and possibly hypogonadotropic hypogonadism.

Thiffault et al. (2015) reported 8 unrelated patients with hypomyelinating leukodystrophy and 13 homozygous or compound heterozygous mutations in the POLR1C gene. All had neurologic abnormalities, including delayed psychomotor development, loss or lack of independent ambulation, abnormal cognition, tremor, ataxia, spasticity, and cerebellar findings. Three had myopia and 3 had dental abnormalities. Six patients were too young to be assessed for hypogonadotropic hypogonadism, and 2 did not have hypogonadism.

Gauquelin et al. (2019) reported 23 patients with hypomyelinating leukodystrophy and 29 different variants (homozygous or compound heterozygous) in the POLR1C gene. Patients too young to comment on hypogonadotropic hypogonadism.
Sources: Literature
Differences of Sex Development v0.313 POLR3B Chirag Patel Classified gene: POLR3B as Green List (high evidence)
Differences of Sex Development v0.313 POLR3B Chirag Patel Gene: polr3b has been classified as Green List (High Evidence).
Differences of Sex Development v0.312 POLR3A Chirag Patel Classified gene: POLR3A as Green List (high evidence)
Differences of Sex Development v0.312 POLR3A Chirag Patel Gene: polr3a has been classified as Green List (High Evidence).
Differences of Sex Development v0.312 POLR3B Chirag Patel gene: POLR3B was added
gene: POLR3B was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3B were set to PubMed: 27512013, 23355746, 22036171, 22036172, 25339210, 33005949, 22855961
Phenotypes for gene: POLR3B were set to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism; OMIM #614381
Review for gene: POLR3B was set to GREEN
Added comment: Hypomyelinating leukodystrophy-8 (HLD8) is an autosomal recessive neurologic disorder characterized by early childhood onset of cerebellar ataxia and mild intellectual disabilities associated with diffuse hypomyelination apparent on brain MRI. Variable features include oligodontia and/or hypogonadotropic hypogonadism. There is considerable inter- and intrafamilial variability.

Multiples families reported with compound heterozygous mutations in POL3RB gene.

Wolf et al. (2014) performed a cross-sectional observational study of 105 patients with 4H syndrome, including 43 with mutations in the POLR3A gene and 62 with mutations in the POLR3B gene. Delayed puberty/HH, in those old enough to assess, occurred in 81% of patients with POLR3A mutations and in 69% of those with POLR3B mutations.
Sources: Literature
Differences of Sex Development v0.311 POLR3A Chirag Patel gene: POLR3A was added
gene: POLR3A was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to PubMed: 21855841, 25339210, 33005949, 22855961
Phenotypes for gene: POLR3A were set to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, OMIM#607694
Review for gene: POLR3A was set to GREEN
Added comment: Hypomyelinating leukodystrophy-7 (HLD7) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive motor decline manifest as spasticity, ataxia, tremor, and cerebellar signs, as well as mild cognitive regression. Other common features may include hypodontia or oligodontia and hypogonadotropic hypogonadism. There is considerable inter- and intrafamilial variability.

Bernard et al. (2011) identified 14 different mutations in the POLR3A gene (homozygous or compound heterozygous state), in 19 patients from 12 families. The mutations were spread throughout the gene, and there were no obvious genotype/phenotype correlations. Immunoblot analysis showed decreased levels of POLR3A protein in fibroblasts from 4 affected individuals, and decreased levels in the cortex and cerebral white matter of another patient, suggesting that loss of function is responsible for the disorder.

Wolf et al. (2014) performed a cross-sectional observational study of 105 patients with 4H syndrome, including 43 with mutations in the POLR3A gene and 62 with mutations in the POLR3B gene. Delayed puberty/HH, in those old enough to assess, occurred in 81% of patients with POLR3A mutations and in 69% of those with POLR3B mutations.
Sources: Literature
Differences of Sex Development v0.310 HARS2 Chirag Patel Classified gene: HARS2 as Green List (high evidence)
Differences of Sex Development v0.310 HARS2 Chirag Patel Gene: hars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.309 HHAT Chirag Patel Classified gene: HHAT as Green List (high evidence)
Differences of Sex Development v0.309 HHAT Chirag Patel Gene: hhat has been classified as Green List (High Evidence).
Differences of Sex Development v0.308 HHAT Chirag Patel gene: HHAT was added
gene: HHAT was added to Differences of Sex Development. Sources: Expert list
Mode of inheritance for gene: HHAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HHAT were set to PMID: 24784881, 33749989, 35045414
Phenotypes for gene: HHAT were set to Nivelon-Nivelon-Mabille syndrome, OMIM:600092
Review for gene: HHAT was set to GREEN
Added comment: 3 individuals from 3 families with 46, XY karyotype and sex reversal, with supportive mouse model reported in 24784881.

PMID:24784881 - Callier et al 2014 - report a family with 2 siblings with Disorder of Sex Development (DSD) and chondrodysplasia (Nivelon-Nivelon-Mabille syndrome). The first sibling (46,XY karyotype) displayed severe dwarfism with generalized chondrodysplasia, a narrow, bell-shaped thorax, micromelia, brachydactyly, severe microcephaly (-7.5 SD at age 16 (PMID:15578577) with cerebellar vermis hypoplasia, facial anomalies, hypoplastic irides, and coloboma of both optic discs. Complete gonadal dysgenesis ( including normal external female genitalia, lack of pubertal development, primary amenorrhea, and hypergonadotrophic hypogonadism) and intellectual disability is also noted. The second sibling (46,XX karyotype) had histologically normal ovaries and similar phenotypic abnormalities including severe dwarfism and generalized chondrodysplasia. Using WES a homozygous missense variant was found NM_001122834:c.860G>T:p.(Gly287Val) in HHAT in the first sibling which is in the conserved MBOAT domain. The parents were heterozygous. They also found that mice lacking functional Hhat show a similar phenotype as the syndromic 46,XY DSD patient including testicular dysgenesis and skeletal defects.

PMID: 33749989 - Pande et al 2021 - report multiple malformations in three pregnancies with a novel biallelic in-frame deletion, c.365_367del; (p.Thr122del), in exon 5 of HHAT in the living proband. She shows severe microphthalmia, microcephaly (−8 SD head circumference at age 7), skeletal dysplasia (narrow bell-shaped thorax, short and angel-shaped epiphyses of hands and feet) and midface retrusion, short columella with a groove at the base, prominent ears, long philtrum, depressed nasal bridge, everted lower lip, and a single central incisor. She also has complete sex reversal (karyotype of 46, XY, normal internal organs including uterus and ovaries.)

PMID: 35045414 - Mazen et al 2022 - report an Egyptian patient with 46,XY DSD (ambiguous genitalia and microcephaly) and a homozygous missense variant in HHAT, which segregated with the phenotype in the family.
Sources: Expert list
Differences of Sex Development v0.307 CTU2 Chirag Patel changed review comment from: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.

PMID:26633546. Affected members of all 3 families have microcephaly, facial dysmorphia and unilateral renal agenesis. 2/3 families have ambiguous genitalia; however, only 1 family had karyotyping done, which showed normal male karyotype (46 XY). 2/3 had congenital heart disease.

PMID: 27480277. Same variant as PMID:26633546. Affected individuals in this extended family have similar phenotype as PMID:26633546. Patient 1: in addition to microcephaly also has renal anomalies (small kidneys) and possible ambiguous genitalia with normal XY karyotype. Patient 2: cousin of patient 1. In addition to microcephaly did not have renal anomalies and nor ambiguous genitalia. Both patients have congenital heart disease.

PMID: 31301155. 5 new cases, all with microcephaly. 4/5 with renal anomalies, 2/5 with ambiguous genitalia, 4/5 congenital heart disease.

Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs.
Sources: Literature; to: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly.

PMID:26633546. Affected members of all 3 families have microcephaly, facial dysmorphia and unilateral renal agenesis. 2/3 families have ambiguous genitalia; however, only 1 family had karyotyping done, which showed normal male karyotype (46 XY). 2/3 had congenital heart disease.

PMID: 27480277. Same variant as PMID:26633546. Affected individuals in this extended family have similar phenotype as PMID:26633546. Patient 1: in addition to microcephaly also has renal anomalies (small kidneys) and possible ambiguous genitalia with normal XY karyotype. Patient 2: cousin of patient 1. In addition to microcephaly did not have renal anomalies and nor ambiguous genitalia. Both patients have congenital heart disease.

PMID: 31301155. 5 new cases, all with microcephaly. 4/5 with renal anomalies, 2/5 with ambiguous genitalia, 4/5 congenital heart disease.

Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs.
Sources: Literature
Differences of Sex Development v0.307 CTU2 Chirag Patel changed review comment from: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.

More than 6 families reported, four had the same founder variant. Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs
Sources: Literature; to: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.

PMID:26633546. Affected members of all 3 families have microcephaly, facial dysmorphia and unilateral renal agenesis. 2/3 families have ambiguous genitalia; however, only 1 family had karyotyping done, which showed normal male karyotype (46 XY). 2/3 had congenital heart disease.

PMID: 27480277. Same variant as PMID:26633546. Affected individuals in this extended family have similar phenotype as PMID:26633546. Patient 1: in addition to microcephaly also has renal anomalies (small kidneys) and possible ambiguous genitalia with normal XY karyotype. Patient 2: cousin of patient 1. In addition to microcephaly did not have renal anomalies and nor ambiguous genitalia. Both patients have congenital heart disease.

PMID: 31301155. 5 new cases, all with microcephaly. 4/5 with renal anomalies, 2/5 with ambiguous genitalia, 4/5 congenital heart disease.

Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs.
Sources: Literature
Differences of Sex Development v0.307 CTU2 Chirag Patel Classified gene: CTU2 as Green List (high evidence)
Differences of Sex Development v0.307 CTU2 Chirag Patel Gene: ctu2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.306 CTU2 Chirag Patel gene: CTU2 was added
gene: CTU2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTU2 were set to PMID: 27480277, 26633546, 31301155, 38348206
Phenotypes for gene: CTU2 were set to DREAM-PL syndrome (Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome), MIM#618142
Review for gene: CTU2 was set to GREEN
Added comment: DREAM-PL syndrome presents with dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. Other anomalies include corpus callosum agenesis or dysgenesis, septal defects, PDA, hypoplastic right ventricle and joint contractures.

More than 6 families reported, four had the same founder variant. Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs
Sources: Literature
Differences of Sex Development v0.305 TWNK Chirag Patel Classified gene: TWNK as Green List (high evidence)
Differences of Sex Development v0.305 TWNK Chirag Patel Gene: twnk has been classified as Green List (High Evidence).
Differences of Sex Development v0.305 TWNK Chirag Patel Classified gene: TWNK as Green List (high evidence)
Differences of Sex Development v0.305 TWNK Chirag Patel Gene: twnk has been classified as Green List (High Evidence).
Differences of Sex Development v0.304 TWNK Chirag Patel gene: TWNK was added
gene: TWNK was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: TWNK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TWNK were set to PMID: 25355836, 31852434, 31455392
Phenotypes for gene: TWNK were set to Perrault syndrome 5; MIM# 616138
Review for gene: TWNK was set to GREEN
Added comment: Perrault syndrome-5 (PRLTS5) is an autosomal recessive disorder characterized by progressive ataxia, axonal neuropathy, hyporeflexia, and abnormal eye movements, accompanied by progressive hearing loss and ovarian dysgenesis.

PMID: 25355836: 4 women from 2 unrelated families with Perrault syndrome-5.
2 sisters in each family presented with primary amenorrhea, lack of secondary sexual characteristics, and gonadal dysgenesis; 2 sisters in 1 family showed streak ovaries. Three of the 4 girls had onset of sensorineural hearing loss at 7 to 8 years of age; the fourth had onset of hearing loss at age 13. All 4 patients developed neurologic involvement in the second or third decades, with features including ataxia, nystagmus, hyporeflexia, and sensory axonal neuropathy with distal sensory impairment. WES identified compound heterozygous variants in each family, but functional studies of the variants were not performed.

PMID: 31852434: female with severe bilateral hypoacusis, severe ataxia, polyneuropathy, lower limb spastic paraparesis with pyramidal signs, and gonadal dysgenesis, and compound heterozygous variants in TWNK gene (but functional studies of the variants were not performed).

PMID: 31455392: 3 siblings from one family with childhood-onset bilateral sensorineural hearing impairment, neurological signs (spinocerebellar ataxia, polyneuropathy), and gonadal dysfunction with early cessation of menses in the 2 females. WES identified compound heterozygous pathogenic mutations in the TWNK gene, which segregated with disease.
,
Sources: Literature
Differences of Sex Development v0.303 MARS2 Chirag Patel Classified gene: MARS2 as Green List (high evidence)
Differences of Sex Development v0.303 MARS2 Chirag Patel Gene: mars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.302 MARS2 Chirag Patel gene: MARS2 was added
gene: MARS2 was added to Differences of Sex Development. Sources: Expert Review
Mode of inheritance for gene: MARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARS2 were set to PMID: 27650058, 21464306, 27087618
Phenotypes for gene: MARS2 were set to Perrault syndrome 2, MIM# 614926
Review for gene: MARS2 was set to GREEN
Added comment: Perrault syndrome-2 (PRLTS2) is an autosomal recessive disorder characterized by sensorineural deafness in both males and females. Affected females have primary amenorrhea, streak gonads (ovarian dysgenesis), and infertility, whereas affected males show normal pubertal development and are fertile. No neurological abnormalities reported.

PMID: 21464306: five affected siblings from one family with three females with ovarian dysgenesis with primary amenorrhea and streak gonads along with sensorineural hearing loss (two males had normal fertility) had two variants in HARS2 with confirmed biparental inheritance. Functional studies showed that the mutations resulted in decreased enzyme activity, and knockdown of the HARS2 homolog in C. elegans caused severe gonadal defects and infertility.

PMID: 27650058: two unrelated probands with Perrault syndrome with profound deafness and secondary amenorrhoea with gonadal dysgenesis were found to have a homozygous variant in HARS2. These probands were not related but were from the same region in Morocco.

PMID: 27087618: 2 siblings in Turkish family with Perrault syndrome (female sibling had with secondary amenorrhea and gonadal dysgenesis) were found to have a homozygous variant in HARS2. No functional work.
Sources: Expert Review
Differences of Sex Development v0.301 HARS2 Chirag Patel gene: HARS2 was added
gene: HARS2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: HARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HARS2 were set to PMID: 27650058, 21464306, 27087618
Phenotypes for gene: HARS2 were set to Perrault syndrome 2, MIM# 614926
Review for gene: HARS2 was set to GREEN
Added comment: Perrault syndrome-2 (PRLTS2) is an autosomal recessive disorder characterized by sensorineural deafness in both males and females. Affected females have primary amenorrhea, streak gonads (ovarian dysgenesis), and infertility, whereas affected males show normal pubertal development and are fertile. No neurological abnormalities reported.

PMID: 21464306: five affected siblings from one family with three females with ovarian dysgenesis with primary amenorrhea and streak gonads along with sensorineural hearing loss (two males had normal fertility) had two variants in HARS2 with confirmed biparental inheritance. Functional studies showed that the mutations resulted in decreased enzyme activity, and knockdown of the HARS2 homolog in C. elegans caused severe gonadal defects and infertility.

PMID: 27650058: two unrelated probands with Perrault syndrome with profound deafness and secondary amenorrhoea with gonadal dysgenesis were found to have a homozygous variant in HARS2. These probands were not related but were from the same region in Morocco.

PMID: 27087618: 2 siblings in Turkish family with Perrault syndrome (female sibling had with secondary amenorrhea and gonadal dysgenesis) were found to have a homozygous variant in HARS2. No functional work.
Sources: Literature
Differences of Sex Development v0.300 LARS2 Chirag Patel Classified gene: LARS2 as Green List (high evidence)
Differences of Sex Development v0.300 LARS2 Chirag Patel Gene: lars2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.299 LARS2 Chirag Patel gene: LARS2 was added
gene: LARS2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: LARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LARS2 were set to PMID: 32423379, 29205794, 23541342, 30737337, 26657938,
Phenotypes for gene: LARS2 were set to Perrault syndrome 4; MIM# 615300
Review for gene: LARS2 was set to GREEN
Added comment: Perrault syndrome-4 (PRLTS4) is an autosomal recessive disorder primarily characterized by early-onset sensorineural hearing loss in both males and females, and premature ovarian failure (POF) due to ovarian dysgenesis in females. Affected individuals may also develop neurologic involvement, including developmental delay or learning difficulties in childhood or onset of progressive movement abnormalities, such as spasticity, in adulthood. Brain imaging may show progressive leukodystrophy. At least 6 families with affected females reported with biallelic variants in LARS2 (mostly missense), which segregated in family. Patient-derived mitochondria showed decreased LARS2 aminoacylation activity (about 50% of controls) in one study.
Sources: Literature
Differences of Sex Development v0.298 ERAL1 Chirag Patel Classified gene: ERAL1 as Amber List (moderate evidence)
Differences of Sex Development v0.298 ERAL1 Chirag Patel Gene: eral1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.297 ERAL1 Chirag Patel reviewed gene: ERAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 28449065; Phenotypes: Perrault syndrome 6, MIM# 617565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.297 RNF216 Zornitza Stark Marked gene: RNF216 as ready
Differences of Sex Development v0.297 RNF216 Zornitza Stark Gene: rnf216 has been classified as Green List (High Evidence).
Differences of Sex Development v0.297 RNF216 Zornitza Stark Classified gene: RNF216 as Green List (high evidence)
Differences of Sex Development v0.297 RNF216 Zornitza Stark Gene: rnf216 has been classified as Green List (High Evidence).
Differences of Sex Development v0.296 RNF216 Zornitza Stark gene: RNF216 was added
gene: RNF216 was added to Differences of Sex Development. Sources: Expert list
Mode of inheritance for gene: RNF216 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF216 were set to 25841028; 23656588
Phenotypes for gene: RNF216 were set to Cerebellar ataxia and hypogonadotropic hypogonadism, MIM# 212840
Review for gene: RNF216 was set to GREEN
Added comment: Gordon Holmes syndrome is an autosomal recessive adult-onset neurodegenerative disorder characterized by progressive cognitive decline, dementia, and variable movement disorders, such as ataxia and chorea. The neurologic phenotype is associated with hypogonadotropic hypogonadism, which can present with amenorrhoea in females.
Sources: Expert list
Differences of Sex Development v0.295 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Nephrotic syndrome, type 14 (MIM#617575) to RENI syndrome (MIM#617575)
Differences of Sex Development v0.294 FKBP4 Bryony Thompson Marked gene: FKBP4 as ready
Differences of Sex Development v0.294 FKBP4 Bryony Thompson Gene: fkbp4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.294 FKBP4 Bryony Thompson Classified gene: FKBP4 as Amber List (moderate evidence)
Differences of Sex Development v0.294 FKBP4 Bryony Thompson Gene: fkbp4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.293 FKBP4 Mark Cleghorn gene: FKBP4 was added
gene: FKBP4 was added to Differences of Sex Development. Sources: Other
Mode of inheritance for gene: FKBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FKBP4 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: FKBP4 were set to unknown
Review for gene: FKBP4 was set to AMBER
Added comment: Rebecca Yarwood, University of Manchester
ESHG presentation 4/6/24, unpublished

Bilalleic FKBP4 w NDD + DSD
Protein has functions in hormone receptor trafficking
FKPB4 highly expressed in stem cell and progenitor cells in gonad and neuronal degeneration

Index case
Severe GDD
abN external genitalia
CV AbN
FBBP4 p.E196*

Via GeneMatcher
7 families (12 individuals)

12/12 severe GDD/ID
9/10 microcephaly
11/12 external genital abnormalities (details not provided)

All w homozygous pLoF variants (mixture of canonical splice, frameshift, nonsense)
Sources: Other
Differences of Sex Development v0.293 RXFP2 Katie Ayers edited their review of gene: RXFP2: Added comment: One individual with bilateral cryptorchidism and infertility had homozygous c.1406delT in RXFP2 (NM_130806.5), leading to a frameshift p.(Phe469Serfs*8). From consanguinous family.

Two affected brothers with homozygous missense variant c.1015A>G in RXFP2 (NM_130806.5) resulting in an amino acid substitution p.(Asn339Asp) with bilateral cryptorchidism.; Changed publications: 37208861; Changed phenotypes: Infertility, cryptorchidism, non-obstructive azoospermia
Differences of Sex Development v0.293 RXFP2 Katie Ayers edited their review of gene: RXFP2: Added comment: Homozygous non-canonical splicing variant by whole-exome sequencing and Sanger sequencing . NM_130806: c.1376-12A > G; Changed rating: GREEN; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Changed publications: 38430325; Changed phenotypes: cryptorchidism and non-obstructive azoospermia; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.293 RXFP2 Katie Ayers commented on gene: RXFP2
Differences of Sex Development v0.293 AXL Zornitza Stark gene: AXL was added
gene: AXL was added to Differences of Sex Development. Sources: Expert Review
Mode of inheritance for gene: AXL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AXL were set to 24476074
Phenotypes for gene: AXL were set to Hypogonadotropic hypogonadism, MONDO:0018555, AXL-related
Review for gene: AXL was set to RED
Added comment: Four variants reported in individuals with KS/IHH. One is non-canonical splice site variant (c.586-6 C>T) but authors demonstrate no abnormal splicing occurs. Remainder are missense. Segregation in one family only: inherited from phenotypically normal parent. Axl null mice demonstrated delay in first estrus and the interval between vaginal opening and first estrus
Sources: Expert Review
Differences of Sex Development v0.292 SEMA3A Zornitza Stark Marked gene: SEMA3A as ready
Differences of Sex Development v0.292 SEMA3A Zornitza Stark Gene: sema3a has been classified as Green List (High Evidence).
Differences of Sex Development v0.292 SEMA3A Zornitza Stark Classified gene: SEMA3A as Green List (high evidence)
Differences of Sex Development v0.292 SEMA3A Zornitza Stark Gene: sema3a has been classified as Green List (High Evidence).
Differences of Sex Development v0.291 SEMA3A Zornitza Stark gene: SEMA3A was added
gene: SEMA3A was added to Differences of Sex Development. Sources: Expert Review
Mode of inheritance for gene: SEMA3A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SEMA3A were set to 28075028; 33369061; 20301509; 21059704; 24124006; 22927827
Phenotypes for gene: SEMA3A were set to Hypogonadotropic hypogonadism 16 with or without anosmia - MIM#614897
Review for gene: SEMA3A was set to GREEN
Added comment: Heterozygous variants associated with isolated GnRH deficiency with or without anosmia (Kallman syndrome like). More severe phenotype with biallelic SEMA3A variants including postnatal short stature and congenital heart defects in 3/3 published, unrelated individuals.

PMID 33369061 Gileta et al 2021 - report x1 patient. Female proband was compound heterozygote for a nonsense variant and a multiexonic deletion of SEMA3A. Presents with postnatal short stature, congenital cardiac anomalies, dysmorphic features, hypogonadotrophic hypogonadism and anosmia.

PMID 28075028 Baumann et al 2017 - report x1 patient. Homozygous LoF variants identified in a proband from a consanguineous Turkish family. Noted at birth to have a high-positioned scapulae, deformed ribs and a lateral clavicular hook. The patient also had upper/lower limb contractures and aberrant right subclavian artery. Mild facial dysmorphism, micropenis and hypogonadotrophic hypogonadism also noted in the first week of life. Postnatal short stature (length 50cm at term birth)

PMID 24124006 Hofmann et al 2013 - first reported biallelic variants in a proband with postnatal short stature, skeletal anomalies of the thorax, congenital heart
defect and camptodactyly
Sources: Expert Review
Differences of Sex Development v0.289 DCAF17 Zornitza Stark Marked gene: DCAF17 as ready
Differences of Sex Development v0.289 DCAF17 Zornitza Stark Gene: dcaf17 has been classified as Green List (High Evidence).
Differences of Sex Development v0.289 DCAF17 Zornitza Stark Classified gene: DCAF17 as Green List (high evidence)
Differences of Sex Development v0.289 DCAF17 Zornitza Stark Gene: dcaf17 has been classified as Green List (High Evidence).
Differences of Sex Development v0.288 DCAF17 Zornitza Stark gene: DCAF17 was added
gene: DCAF17 was added to Differences of Sex Development. Sources: Expert Review
Mode of inheritance for gene: DCAF17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCAF17 were set to 19026396; 20507343; 35002959; 34877714; 34732557; 34590781
Phenotypes for gene: DCAF17 were set to Woodhouse-Sakati syndrome, MIM# 241080
Review for gene: DCAF17 was set to GREEN
Added comment: Well established gene-disease association. Hypogonadism is a key feature.
Sources: Expert Review
Differences of Sex Development v0.287 CLPP Zornitza Stark Marked gene: CLPP as ready
Differences of Sex Development v0.287 CLPP Zornitza Stark Gene: clpp has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.287 CLPP Zornitza Stark Classified gene: CLPP as Amber List (moderate evidence)
Differences of Sex Development v0.287 CLPP Zornitza Stark Gene: clpp has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.286 CLPP Zornitza Stark gene: CLPP was added
gene: CLPP was added to Differences of Sex Development. Sources: Expert Review
Mode of inheritance for gene: CLPP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLPP were set to 23541340; 25956234; 26970254; 27087618; 27650058; 27650058; 27899912
Phenotypes for gene: CLPP were set to Perrault syndrome 3, MIM# 614129
Review for gene: CLPP was set to AMBER
Added comment: Multiple families with Perrault syndrome, HH is an inconsistent feature.

PMID: 23541340, describes 3 consanguineous Pakistani families (PDF1, PKDF291 and DEM4395), all affected individuals had sensorineural hearing loss. Family PDF1: 3 affected sisters, 1/3 had delayed puberty, streak ovaries and hormone levels consistant with hypogonadotropic hypogonadism, 2/3 had incipient POF and 1/3 had white matter phenotype. All three had epilepsy, short stature, microcephaly (< 3 percentile), moderate learning difficulties and ataxia.
Family PKDF291: 4 affected females with primary amenorrhea and hypogonadotropic hypogonadism. 3/4 had rudimentary uterus and small ovaries, 1/4 had small uterus and normal sized ovaries. No learning disabilities, microcephaly, short stature, epilepsy or neurological deficiet in all affected females.
Family DEM4395: 1 affected male and 2 affected females. All females had normal periods but their hormone profiles were not investigated. Aside from hearing loss there were no other self reported medical problems.

PMID: 25956234. Consanguineous Saudi family with 1 affected male and 1 affected female. Both patients have hearing loss, growth retardation and mental retardation, spastic diplegia and mild-severe white matter loss. No seizures were described in the patients. There is a third sibling (8 months) with the same variant; however, he did not show any of the phenotypes seen in his siblings but he is under regular checkups from a clinical team.

PMID:26970254. Consanguineous family of Arabic descent. Proband with 4 unaffected siblings and parents. Proband has hearing loss, azoospermia, no neurological symptoms other than the foot drop (neurophysiology revealed a sensory-motor demyelinative axonal peripheral neuropathy of the lower limbs). Father has cerebellar ataxia (cause unknown).

PMID: 27087618. Non-consanguineous Turkish family; however, parents are from the same village. 2 affected siblings (1 male, 1 female). Sister has secondary amenorrhea, hearing loss, no ovaries detected, hypogonadotropic hypogonadism, no neurological problems. Brother has hearing loss but no other problems.

PMID: 27650058. Consanguineous Algerian family with 2 affected females. Both have hearing loss and secondary amenorrhea, but no other neurological symptoms.

PMID: 27899912. 3 affected families, with 5 affected individuals (all males). All had congenital deafness, psychomotor retardation, white matter phenotype and short stature. Patients were not tested for infertility.
Sources: Expert Review
Differences of Sex Development v0.285 CCDC141 Zornitza Stark Marked gene: CCDC141 as ready
Differences of Sex Development v0.285 CCDC141 Zornitza Stark Gene: ccdc141 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.285 CCDC141 Zornitza Stark Classified gene: CCDC141 as Amber List (moderate evidence)
Differences of Sex Development v0.285 CCDC141 Zornitza Stark Gene: ccdc141 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.284 CCDC141 Zornitza Stark gene: CCDC141 was added
gene: CCDC141 was added to Differences of Sex Development. Sources: Expert Review
Mode of inheritance for gene: CCDC141 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CCDC141 were set to 251920460; 28324054; 32520725; 27014940
Phenotypes for gene: CCDC141 were set to congenital hypogonadotropic hypogonadism, MONDO:0015770, CCDC141-related
Review for gene: CCDC141 was set to AMBER
Added comment: PMID: 251920460 describes 2 affected siblings from a consanguineous family with anosmic HH, who had homozygous variant in FEZF1 (Amber gene on this panel) and also homozyous for variant in CCDC141.

PMID: 28324054 describes the above case and also 3 new cases (all had normal sense of smell and HH). Family 2: compound het for CCDC141 and heterozygous for DMXL2 variant. Family 3: heterozygous for CCDC141 variant and heterozygous for variants in 3 other genes (NR5A2, FSHB - Green on HH panel, IGSF10). Family 4: affected patient was heterozygous for CCDC141 variant, which the father also carried but father was unaffected.

PMID: 32520725 describes a large Chinese cohort with congenital HH looking at the contribution of CCDC141 to the disease. 12 probands had variants CCDC141 and 9 of these probands had variants in other HH-related genes (inluding PCSK1, ANOS1, PROKR2, AXL, SOX10, HS6ST1, PNPLA6 and FGFR1). The authors concluded that CCDC141 variants alone is not sufficient to cause HH.

PMID: 27014940 talks about a ccdc141 knockdown mouse model reduces GnRH neuronal migration.

Overall, insufficient evidence for gene-disease association; may be a modifier.
Sources: Expert Review
Differences of Sex Development v0.283 NR2F2 Zornitza Stark Phenotypes for gene: NR2F2 were changed from 46,XX disorder of sex development (DSD) and congenital heart defects to 46XX sex reversal 5, MIM# 618901
Differences of Sex Development v0.282 NR2F2 Zornitza Stark edited their review of gene: NR2F2: Changed phenotypes: 46XX sex reversal 5, MIM# 618901
Differences of Sex Development v0.282 SOX11 Zornitza Stark Marked gene: SOX11 as ready
Differences of Sex Development v0.282 SOX11 Zornitza Stark Gene: sox11 has been classified as Green List (High Evidence).
Differences of Sex Development v0.282 SOX11 Zornitza Stark Classified gene: SOX11 as Green List (high evidence)
Differences of Sex Development v0.282 SOX11 Zornitza Stark Gene: sox11 has been classified as Green List (High Evidence).
Differences of Sex Development v0.281 SOX11 Zornitza Stark gene: SOX11 was added
gene: SOX11 was added to Differences of Sex Development. Sources: Expert Review
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX11 were set to 29459093; 24886874; 33086258; 33785884; 35642566; 35341651
Phenotypes for gene: SOX11 were set to Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, MIM# 615866
Review for gene: SOX11 was set to GREEN
Added comment: Over 40 individuals reported, e.g. PMID 35341651. The phenotype that has emerged over time is distinct from patients with mutations in ARID1B (614556) and Coffin-Siris syndrome-1 (135900). Patients with IDDMOH tend to be microcephalic and have ocular motor apraxia, abnormal eye morphology, or hypogonadotropic hypogonadism.
Sources: Expert Review
Differences of Sex Development v0.280 SLC20A1 Zornitza Stark Marked gene: SLC20A1 as ready
Differences of Sex Development v0.280 SLC20A1 Zornitza Stark Gene: slc20a1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.280 SLC20A1 Zornitza Stark Phenotypes for gene: SLC20A1 were changed from Bladder-Exstrophy-Epispadias Complex (BEEC) to Bladder-Exstrophy-Epispadias Complex (BEEC), MONDO:0017919, SLC20A1-related
Differences of Sex Development v0.279 PTCH1 Zornitza Stark Marked gene: PTCH1 as ready
Differences of Sex Development v0.279 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.279 PTCH1 Zornitza Stark Classified gene: PTCH1 as Amber List (moderate evidence)
Differences of Sex Development v0.279 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.278 SLC20A1 Chirag Patel Classified gene: SLC20A1 as Green List (high evidence)
Differences of Sex Development v0.278 SLC20A1 Chirag Patel Gene: slc20a1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.277 SLC20A1 Chirag Patel gene: SLC20A1 was added
gene: SLC20A1 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: SLC20A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC20A1 were set to PMID: 32850778, 27013921
Phenotypes for gene: SLC20A1 were set to Bladder-Exstrophy-Epispadias Complex (BEEC)
Review for gene: SLC20A1 was set to GREEN
gene: SLC20A1 was marked as current diagnostic
Added comment: Three individuals with BEEC and animal model supporting role of this gene in urinary tract and urorectal development.
Sources: Literature
Differences of Sex Development v0.276 PTCH1 Chirag Patel gene: PTCH1 was added
gene: PTCH1 was added to Differences of Sex Development. Sources: Other
Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTCH1 were set to Bladder exstrophy and epispadias complex (BEEC)
Review for gene: PTCH1 was set to AMBER
Added comment: ESHG 2023:
9 individuals with BEEC (WES/Sanger) with 9 x rare HTZ variants in PTCH1 (2 de novo, 7 inherited unaffected parent). No clinical features of Gorlin syndrome and variants not seen in Gorlin syndrome.

Zebrafish models:
a) knock out and knock in (1 missense variant) models showed no phenotype
b) co-injection of WT and missense variant led to altered cloaca on D5.
Proposed mechanism is dominant negative effect.
Sources: Other
Differences of Sex Development v0.276 PTCH1 Chirag Patel gene: PTCH1 was added
gene: PTCH1 was added to Differences of Sex Development. Sources: Other
Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTCH1 were set to Bladder exstrophy and epispadias complex (BEEC)
Review for gene: PTCH1 was set to AMBER
Added comment: ESHG 2023:
9 individuals with BEEC (WES/Sanger) with 9 x rare HTZ variants in PTCH1 (2 de novo, 7 inherited unaffected parent). No clinical features of Gorlin syndrome and variants not seen in Gorlin syndrome.

Zebrafish models:
a) knock out and knock in (1 missense variant) models showed no phenotype
b) co-injection of WT and missense variant led to altered cloaca on D5.
Proposed mechanism is dominant negative effect.
Sources: Other
Differences of Sex Development v0.275 SART3 Krithika Murali Classified gene: SART3 as Green List (high evidence)
Differences of Sex Development v0.275 SART3 Krithika Murali Gene: sart3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.274 SART3 Krithika Murali Marked gene: SART3 as ready
Differences of Sex Development v0.274 SART3 Krithika Murali Gene: sart3 has been removed from the panel.
Differences of Sex Development v0.274 SART3 Daniel Flanagan gene: SART3 was added
gene: SART3 was added to Differences of Sex Development. Sources: Expert list
Mode of inheritance for gene: SART3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SART3 were set to PMID: 37296101
Phenotypes for gene: SART3 were set to Neurodevelopmental disorder (MONDO#0700092), SART3-related; 46,XY disorder of sex development (MONDO:0020040), SART3-related
Review for gene: SART3 was set to GREEN
Added comment: Nine individuals from six families presenting with intellectual disability, global developmental delay, a subset of brain anomalies, together with gonadal dysgenesis in 46,XY individuals. Additionally, two individuals had seizures and two had epileptiform activity reported on EEG.

Human induced pluripotent stem cells carrying patient variants in SART3 show disruption to multiple signalling pathways, upregulation of spliceosome components and demonstrate aberrant gonadal and neuronal differentiation in vitro.
Sources: Expert list
Differences of Sex Development v0.274 DAAM2 Zornitza Stark Marked gene: DAAM2 as ready
Differences of Sex Development v0.274 DAAM2 Zornitza Stark Gene: daam2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.274 DAAM2 Zornitza Stark Classified gene: DAAM2 as Green List (high evidence)
Differences of Sex Development v0.274 DAAM2 Zornitza Stark Gene: daam2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.273 DAAM2 Zornitza Stark gene: DAAM2 was added
gene: DAAM2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: DAAM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAAM2 were set to 36972684
Phenotypes for gene: DAAM2 were set to Androgen insensitivity syndrome, MONDO:0019154, DAAM2-related
Review for gene: DAAM2 was set to GREEN
Added comment: 6 unrelated individuals with extensive functional data.
Sources: Literature
Differences of Sex Development v0.272 ARHGAP35 Zornitza Stark Marked gene: ARHGAP35 as ready
Differences of Sex Development v0.272 ARHGAP35 Zornitza Stark Gene: arhgap35 has been classified as Green List (High Evidence).
Differences of Sex Development v0.272 ARHGAP35 Zornitza Stark Phenotypes for gene: ARHGAP35 were changed from Idiopathic hypogonadotropic hypogonadism, no OMIM # to Hypogonadotropic hypogonadism, MONDO:0015770, ARHGAP35-related
Differences of Sex Development v0.271 ARHGAP35 Zornitza Stark reviewed gene: ARHGAP35: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypogonadotropic hypogonadism, MONDO:0015770, ARHGAP35-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.271 ARHGAP35 Chirag Patel Classified gene: ARHGAP35 as Green List (high evidence)
Differences of Sex Development v0.271 ARHGAP35 Chirag Patel Gene: arhgap35 has been classified as Green List (High Evidence).
Differences of Sex Development v0.270 ARHGAP35 Chirag Patel gene: ARHGAP35 was added
gene: ARHGAP35 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: ARHGAP35 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARHGAP35 were set to PMID: 36178483
Phenotypes for gene: ARHGAP35 were set to Idiopathic hypogonadotropic hypogonadism, no OMIM #
Review for gene: ARHGAP35 was set to GREEN
Added comment: 12 patients with idiopathic hypogonadotropic hypogonadism. Rare protein-truncating variants (n = 5) and missense variants (n = 7) found in the RhoGAP domain of ARHGAP35 gene. Zebrafish modeling using gnrh3:egfp phenotype assessment showed that mutant larvae with deficient arhgap35a (predominant ARHGAP35 paralog in zebrafish brain), displayed decreased GnRH3-GFP+ neuronal area, a readout for IHH. In vitro GAP activity studies showed that 1 rare missense variant (Arg1284Trp) had decreased GAP activity.
Sources: Literature
Differences of Sex Development v0.269 Zornitza Stark HPO terms changed from to Abnormality of the genital system, HP:0000078
List of related panels changed from to Abnormality of the genital system; HP:0000078
Differences of Sex Development v0.268 CYP17A1 Zornitza Stark Tag treatable tag was added to gene: CYP17A1.
Differences of Sex Development v0.268 CYP11B1 Zornitza Stark Tag treatable tag was added to gene: CYP11B1.
Differences of Sex Development v0.268 KCNK3 Zornitza Stark Marked gene: KCNK3 as ready
Differences of Sex Development v0.268 KCNK3 Zornitza Stark Gene: kcnk3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.268 KCNK3 Zornitza Stark Classified gene: KCNK3 as Green List (high evidence)
Differences of Sex Development v0.268 KCNK3 Zornitza Stark Gene: kcnk3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.267 KCNK3 Krithika Murali gene: KCNK3 was added
gene: KCNK3 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: KCNK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNK3 were set to 36195757
Phenotypes for gene: KCNK3 were set to Neurodevelopmental disorder, MONDO:0700092, KCNK3-related; developmental delay with sleep apnoea (DDSA)
Review for gene: KCNK3 was set to GREEN
Added comment: PMID 36195757 Sörmann et al 2022 report 9 unrelated individuals with de novo heterozygous KCNK3 missense variants (21 weeks to 25 years old). All 8 living probands (3-25 years) had hypotonia, global developmental delay, central and/or obstructive sleep apnoea and feeding difficulties. 7/9 probands had additional anomalies including microcephaly (at least 3/9), arthrogryposis/flexion contractures/foot deformities (7/9), scoliosis, cleft palate (2/9), and ambiguous genitalia/undescended testes (5/6) and dysmorphism. IUGR reported in 3/9 probands and polyhdramnios in 2/9.

KCNK3 encodes the TASK-1 K2P channel expressed throughout the central nervous system. All identified variants clustered near the X-gate and are involved in inter- or intra-subunit interaction likely to hold the X-gate closed. Individuals with variants located in the M2 transmembrane helix had a more severe phenotype than those with variants in the M4 helix. Functional studies support a gain of function disease mechanism with increased channel activation. TASK-1 K+ channel inhibitors (some in clinical use) have been raised as a possible therapeutic strategy.

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Heterozygous LoF variants associated with a different disorder - primary pulmonary arterial hypertension
Sources: Literature
Differences of Sex Development v0.267 LHX3 Zornitza Stark Tag treatable tag was added to gene: LHX3.
Differences of Sex Development v0.267 LEPR Zornitza Stark Tag treatable tag was added to gene: LEPR.
Tag clinical trial tag was added to gene: LEPR.
Differences of Sex Development v0.267 NDNF Elena Savva Phenotypes for gene: NDNF were changed from Hypogonadotropic hypogonadism 25 with anosmia MIM#618841 to Hypogonadotropic hypogonadism 25 with anosmia MIM#618841
Differences of Sex Development v0.266 NDNF Elena Savva Phenotypes for gene: NDNF were changed from Congenital hypogonadotropic hypogonadism (CHH) to Hypogonadotropic hypogonadism 25 with anosmia MIM#618841
Differences of Sex Development v0.266 NDNF Elena Savva Classified gene: NDNF as Amber List (moderate evidence)
Differences of Sex Development v0.266 NDNF Elena Savva Gene: ndnf has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.265 NDNF Elena Savva reviewed gene: NDNF: Rating: AMBER; Mode of pathogenicity: None; Publications: 31883645; Phenotypes: Hypogonadotropic hypogonadism 25 with anosmia MIM#618841; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Differences of Sex Development v0.265 PBX1 Bryony Thompson Phenotypes for gene: PBX1 were changed from 46, XY gonadal dysgenesis to 46, XY gonadal dysgenesis; congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay MONDO:0060549
Differences of Sex Development v0.264 PBX1 Bryony Thompson Publications for gene: PBX1 were set to 31302614; 31058389
Differences of Sex Development v0.263 PBX1 Bryony Thompson Classified gene: PBX1 as Green List (high evidence)
Differences of Sex Development v0.263 PBX1 Bryony Thompson Gene: pbx1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.262 PBX1 Bryony Thompson reviewed gene: PBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35451537, 31302614, 31058389, 32141698; Phenotypes: congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay MONDO:0060549; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.262 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from congenital hypogonadotropic hypogonadism, MONDO:0015770 to Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761
Differences of Sex Development v0.261 PRDM13 Zornitza Stark edited their review of gene: PRDM13: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.261 PRDM13 Zornitza Stark reviewed gene: PRDM13: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.261 MAP3K1 Zornitza Stark Marked gene: MAP3K1 as ready
Differences of Sex Development v0.261 MAP3K1 Zornitza Stark Gene: map3k1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.261 MAP3K1 Zornitza Stark Phenotypes for gene: MAP3K1 were changed from to 46XY sex reversal 6 (MIM#613762)
Differences of Sex Development v0.260 MAP3K1 Zornitza Stark Publications for gene: MAP3K1 were set to
Differences of Sex Development v0.259 MAP3K1 Zornitza Stark Mode of inheritance for gene: MAP3K1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.258 MAP3K1 Zornitza Stark reviewed gene: MAP3K1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21129722, 32986312; Phenotypes: 46XY sex reversal 6 (MIM#613762); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.258 DUSP6 Zornitza Stark Marked gene: DUSP6 as ready
Differences of Sex Development v0.258 DUSP6 Zornitza Stark Gene: dusp6 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.258 DUSP6 Zornitza Stark Phenotypes for gene: DUSP6 were changed from to Hypogonadotropic hypogonadism 19 with or without anosmia - MIM#615269
Differences of Sex Development v0.257 DUSP6 Zornitza Stark Publications for gene: DUSP6 were set to
Differences of Sex Development v0.256 DUSP6 Zornitza Stark Mode of inheritance for gene: DUSP6 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.255 DUSP6 Zornitza Stark Classified gene: DUSP6 as Red List (low evidence)
Differences of Sex Development v0.255 DUSP6 Zornitza Stark Gene: dusp6 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.254 HSD3B2 Zornitza Stark Marked gene: HSD3B2 as ready
Differences of Sex Development v0.254 HSD3B2 Zornitza Stark Gene: hsd3b2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.254 HSD3B2 Zornitza Stark Phenotypes for gene: HSD3B2 were changed from to Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency, MIM# 201810
Differences of Sex Development v0.253 HSD3B2 Zornitza Stark Publications for gene: HSD3B2 were set to
Differences of Sex Development v0.252 HSD3B2 Zornitza Stark Mode of inheritance for gene: HSD3B2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.251 HSD3B2 Zornitza Stark reviewed gene: HSD3B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 1363812, 18252794; Phenotypes: Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency, MIM# 201810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.251 DUSP6 Krithika Murali reviewed gene: DUSP6: Rating: RED; Mode of pathogenicity: None; Publications: 23643382, 32389901; Phenotypes: Hypogonadotropic hypogonadism 19 with or without anosmia - MIM#615269; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.251 RSPO1 Zornitza Stark Marked gene: RSPO1 as ready
Differences of Sex Development v0.251 RSPO1 Zornitza Stark Gene: rspo1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.251 RSPO1 Zornitza Stark Phenotypes for gene: RSPO1 were changed from to Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal MIM#610644; Palmoplantar hyperkeratosis and true hermaphroditism MIM#610644
Differences of Sex Development v0.250 RSPO1 Zornitza Stark Publications for gene: RSPO1 were set to
Differences of Sex Development v0.249 RSPO1 Zornitza Stark Mode of inheritance for gene: RSPO1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.248 RSPO1 Belinda Chong reviewed gene: RSPO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17041600, 18085567, 18250098, 18250097; Phenotypes: Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal MIM#610644, Palmoplantar hyperkeratosis and true hermaphroditism MIM#610644; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Differences of Sex Development v0.248 SRD5A2 Zornitza Stark Marked gene: SRD5A2 as ready
Differences of Sex Development v0.248 SRD5A2 Zornitza Stark Gene: srd5a2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.248 SRD5A2 Zornitza Stark Phenotypes for gene: SRD5A2 were changed from to Pseudovaginal perineoscrotal hypospadias, MIM# 264600
Differences of Sex Development v0.247 SRD5A2 Zornitza Stark Publications for gene: SRD5A2 were set to
Differences of Sex Development v0.246 SRD5A2 Zornitza Stark Mode of inheritance for gene: SRD5A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.245 SRD5A2 Zornitza Stark reviewed gene: SRD5A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 1944596, 12843198, 35331321, 35154247, 35135181; Phenotypes: Pseudovaginal perineoscrotal hypospadias, MIM# 264600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.245 STAR Zornitza Stark Marked gene: STAR as ready
Differences of Sex Development v0.245 STAR Zornitza Stark Gene: star has been classified as Green List (High Evidence).
Differences of Sex Development v0.245 STAR Zornitza Stark Phenotypes for gene: STAR were changed from to Lipoid adrenal hyperplasia (MIM#201710)
Differences of Sex Development v0.244 STAR Zornitza Stark Publications for gene: STAR were set to
Differences of Sex Development v0.243 STAR Zornitza Stark Mode of inheritance for gene: STAR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.242 STAR Zornitza Stark reviewed gene: STAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 7892608, 8634702; Phenotypes: Lipoid adrenal hyperplasia (MIM#201710); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.242 PPP2R3C Zornitza Stark Marked gene: PPP2R3C as ready
Differences of Sex Development v0.242 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
Differences of Sex Development v0.242 PPP2R3C Zornitza Stark Publications for gene: PPP2R3C were set to PMID: 30893644, 34714774, 34750818
Differences of Sex Development v0.241 PPP2R3C Chirag Patel Classified gene: PPP2R3C as Green List (high evidence)
Differences of Sex Development v0.241 PPP2R3C Chirag Patel Gene: ppp2r3c has been classified as Green List (High Evidence).
Differences of Sex Development v0.240 PPP2R3C Chirag Patel gene: PPP2R3C was added
gene: PPP2R3C was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP2R3C were set to PMID: 30893644, 34714774, 34750818
Phenotypes for gene: PPP2R3C were set to Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, OMIM # 618419
Review for gene: PPP2R3C was set to GREEN
Added comment: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay.

11 unrelated families with syndromic complete gonadal dysgenesis. 9 families had 46,XY females with complete gonadal dysgenesis, but 2 families had 46,XX patients with hypergonadotropic hypogonadism, nonvisualized gonads, primary amenorrhea, and absence of secondary sexual characteristics. Variants segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility.
Sources: Literature
Differences of Sex Development v0.239 NHLH2 Zornitza Stark Marked gene: NHLH2 as ready
Differences of Sex Development v0.239 NHLH2 Zornitza Stark Gene: nhlh2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.239 NHLH2 Zornitza Stark gene: NHLH2 was added
gene: NHLH2 was added to Differences of Sex Development. Sources: Expert Review
Mode of inheritance for gene: NHLH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLH2 were set to 35066646
Phenotypes for gene: NHLH2 were set to Hypogonadotropic hypogonadism 27 without anosmia , MIM# 619755
Review for gene: NHLH2 was set to RED
Added comment: Single individual reported homozygous for a missense variant in this gene. Two other individuals heterozygous for missense variants identified as part of this cohort; however, had alternative diagnoses.
Sources: Expert Review
Differences of Sex Development v0.238 TCF12 Zornitza Stark Phenotypes for gene: TCF12 were changed from Kallmann syndrome to Hypogonadotropic hypogonadism 26 with or without anosmia, MIM# 619718; Kallmann syndrome
Differences of Sex Development v0.237 TCF12 Zornitza Stark edited their review of gene: TCF12: Changed phenotypes: Hypogonadotropic hypogonadism 26 with or without anosmia, MIM# 619718, Kallmann syndrome
Differences of Sex Development v0.237 MAMLD1 Zornitza Stark Marked gene: MAMLD1 as ready
Differences of Sex Development v0.237 MAMLD1 Zornitza Stark Gene: mamld1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.237 MAMLD1 Zornitza Stark Phenotypes for gene: MAMLD1 were changed from to Hypospadias 2 (MIM#300758)
Differences of Sex Development v0.236 MAMLD1 Zornitza Stark Publications for gene: MAMLD1 were set to
Differences of Sex Development v0.235 MAMLD1 Zornitza Stark Mode of inheritance for gene: MAMLD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.234 MAMLD1 Teresa Zhao reviewed gene: MAMLD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26815876, PMID: 31555317, PMID: 32690052; Phenotypes: Hypospadias 2 (MIM#300758); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.234 PRDM13 Zornitza Stark Tag founder tag was added to gene: PRDM13.
Differences of Sex Development v0.234 PRDM13 Seb Lunke Marked gene: PRDM13 as ready
Differences of Sex Development v0.234 PRDM13 Seb Lunke Gene: prdm13 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.234 PRDM13 Seb Lunke Classified gene: PRDM13 as Amber List (moderate evidence)
Differences of Sex Development v0.234 PRDM13 Seb Lunke Gene: prdm13 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.233 PRDM13 Seb Lunke gene: PRDM13 was added
gene: PRDM13 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: PRDM13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM13 were set to 34730112
Phenotypes for gene: PRDM13 were set to congenital hypogonadotropic hypogonadism, MONDO:0015770
Review for gene: PRDM13 was set to AMBER
Added comment: Recessive disease causing ID and DSD described in three supposedly unrelated families (2 consanguine), but all are from Malta, and all share the same 13bp deletion spanning an exon-intron boundary. Mouse KO is embryonically lethal, and tissue specific KO failed to replicate many of the patients phenotypes, other than hypoplasia of the cerebellar vermis and hemispheres at P21.
Sources: Literature
Differences of Sex Development v0.232 CYP17A1 Zornitza Stark Marked gene: CYP17A1 as ready
Differences of Sex Development v0.232 CYP17A1 Zornitza Stark Gene: cyp17a1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.232 CYP17A1 Zornitza Stark Phenotypes for gene: CYP17A1 were changed from to 17-alpha-hydroxylase/17,20-lyase deficiency, MIM# 202110
Differences of Sex Development v0.231 CYP17A1 Zornitza Stark Publications for gene: CYP17A1 were set to
Differences of Sex Development v0.230 CYP17A1 Zornitza Stark Mode of inheritance for gene: CYP17A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.229 CYP17A1 Zornitza Stark reviewed gene: CYP17A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 2843762, 14671162, 2026124; Phenotypes: 17-alpha-hydroxylase/17,20-lyase deficiency, MIM# 202110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.229 CYP11B1 Zornitza Stark Marked gene: CYP11B1 as ready
Differences of Sex Development v0.229 CYP11B1 Zornitza Stark Gene: cyp11b1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.229 CYP11B1 Zornitza Stark Phenotypes for gene: CYP11B1 were changed from to Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency, MIM# 202010
Differences of Sex Development v0.228 CYP11B1 Zornitza Stark Publications for gene: CYP11B1 were set to
Differences of Sex Development v0.227 CYP11B1 Zornitza Stark Mode of inheritance for gene: CYP11B1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.226 CYP11B1 Zornitza Stark reviewed gene: CYP11B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8768848; Phenotypes: Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency, MIM# 202010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.226 CYP11A1 Zornitza Stark Marked gene: CYP11A1 as ready
Differences of Sex Development v0.226 CYP11A1 Zornitza Stark Gene: cyp11a1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.226 CYP11A1 Zornitza Stark Phenotypes for gene: CYP11A1 were changed from to Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete, MIM# 613743
Differences of Sex Development v0.225 CYP11A1 Zornitza Stark Publications for gene: CYP11A1 were set to
Differences of Sex Development v0.224 CYP11A1 Zornitza Stark Mode of inheritance for gene: CYP11A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.223 CYP11A1 Zornitza Stark reviewed gene: CYP11A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12161514, 16705068, 18182448, 28425981; Phenotypes: Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete, MIM# 613743; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.223 HSD17B3 Zornitza Stark Marked gene: HSD17B3 as ready
Differences of Sex Development v0.223 HSD17B3 Zornitza Stark Gene: hsd17b3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.223 HSD17B3 Zornitza Stark Phenotypes for gene: HSD17B3 were changed from to Pseudohermaphroditism, male, with gynecomastia MIM#264300
Differences of Sex Development v0.222 HSD17B3 Zornitza Stark Publications for gene: HSD17B3 were set to
Differences of Sex Development v0.221 HSD17B3 Zornitza Stark Mode of inheritance for gene: HSD17B3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.220 HSD17B3 Zornitza Stark reviewed gene: HSD17B3: Rating: GREEN; Mode of pathogenicity: None; Publications: 8550739, 11158067; Phenotypes: Pseudohermaphroditism, male, with gynecomastia MIM#264300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.220 ANOS1 Zornitza Stark Marked gene: ANOS1 as ready
Differences of Sex Development v0.220 ANOS1 Zornitza Stark Gene: anos1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.220 ANOS1 Zornitza Stark Phenotypes for gene: ANOS1 were changed from to Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1), MIM# 308700
Differences of Sex Development v0.219 ANOS1 Zornitza Stark Publications for gene: ANOS1 were set to
Differences of Sex Development v0.218 ANOS1 Zornitza Stark Mode of inheritance for gene: ANOS1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.217 ANOS1 Zornitza Stark reviewed gene: ANOS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 1594017, 8504298, 8989261; Phenotypes: Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1), MIM# 308700; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.217 COG6 Zornitza Stark Marked gene: COG6 as ready
Differences of Sex Development v0.217 COG6 Zornitza Stark Gene: cog6 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.217 COG6 Zornitza Stark Classified gene: COG6 as Amber List (moderate evidence)
Differences of Sex Development v0.217 COG6 Zornitza Stark Gene: cog6 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.216 COG6 Zornitza Stark gene: COG6 was added
gene: COG6 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: COG6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG6 were set to 33394555; 32683677
Phenotypes for gene: COG6 were set to Congenital disorder of glycosylation, type IIl, MIM# 614576
Review for gene: COG6 was set to AMBER
Added comment: <20 families reported with this type of CDG; two families with multi-system features including significant DSD.
Sources: Literature
Differences of Sex Development v0.215 CPE Zornitza Stark Marked gene: CPE as ready
Differences of Sex Development v0.215 CPE Zornitza Stark Gene: cpe has been classified as Green List (High Evidence).
Differences of Sex Development v0.215 CPE Zornitza Stark Classified gene: CPE as Green List (high evidence)
Differences of Sex Development v0.215 CPE Zornitza Stark Gene: cpe has been classified as Green List (High Evidence).
Differences of Sex Development v0.214 CPE Zornitza Stark gene: CPE was added
gene: CPE was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: CPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPE were set to 26120850; 32936766; 34383079
Phenotypes for gene: CPE were set to Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326
Review for gene: CPE was set to GREEN
Added comment: 8 individuals from 5 unrelated families reported.
Sources: Literature
Differences of Sex Development v0.213 CDKN1C Zornitza Stark Marked gene: CDKN1C as ready
Differences of Sex Development v0.213 CDKN1C Zornitza Stark Gene: cdkn1c has been classified as Green List (High Evidence).
Differences of Sex Development v0.213 CDKN1C Zornitza Stark Phenotypes for gene: CDKN1C were changed from to IMAGe syndrome, MIM# 614732
Differences of Sex Development v0.212 CDKN1C Zornitza Stark Publications for gene: CDKN1C were set to
Differences of Sex Development v0.211 CDKN1C Zornitza Stark Mode of pathogenicity for gene: CDKN1C was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Differences of Sex Development v0.210 CDKN1C Zornitza Stark Mode of inheritance for gene: CDKN1C was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Differences of Sex Development v0.209 CDKN1C Zornitza Stark reviewed gene: CDKN1C: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 22634751, 33076988, 31976094, 31497289; Phenotypes: IMAGe syndrome, MIM# 614732; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Differences of Sex Development v0.209 IGF2 Zornitza Stark Marked gene: IGF2 as ready
Differences of Sex Development v0.209 IGF2 Zornitza Stark Gene: igf2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.209 IGF2 Zornitza Stark Classified gene: IGF2 as Green List (high evidence)
Differences of Sex Development v0.209 IGF2 Zornitza Stark Gene: igf2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.208 IGF2 Elena Savva gene: IGF2 was added
gene: IGF2 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: IGF2 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: IGF2 were set to PMID: 31544945
Phenotypes for gene: IGF2 were set to Silver-Russell syndrome 3 MIM#616489
Review for gene: IGF2 was set to GREEN
Added comment: PMID: 31544945 - 60% of patients reported some form of DSD including hypospadias, cryptochidism, abnormal scrotum etc.
Sources: Literature
Differences of Sex Development v0.208 SEMA3F Zornitza Stark Marked gene: SEMA3F as ready
Differences of Sex Development v0.208 SEMA3F Zornitza Stark Gene: sema3f has been classified as Green List (High Evidence).
Differences of Sex Development v0.208 PLXNA3 Zornitza Stark Marked gene: PLXNA3 as ready
Differences of Sex Development v0.208 PLXNA3 Zornitza Stark Gene: plxna3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.208 PLXNA3 Chirag Patel Classified gene: PLXNA3 as Green List (high evidence)
Differences of Sex Development v0.208 PLXNA3 Chirag Patel Gene: plxna3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.208 SEMA3F Chirag Patel Classified gene: SEMA3F as Green List (high evidence)
Differences of Sex Development v0.208 SEMA3F Chirag Patel Gene: sema3f has been classified as Green List (High Evidence).
Differences of Sex Development v0.207 SEMA3F Chirag Patel gene: SEMA3F was added
gene: SEMA3F was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: SEMA3F was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEMA3F were set to PMID: 33495532
Phenotypes for gene: SEMA3F were set to Hypogonadotropic hypogonadism
Review for gene: SEMA3F was set to GREEN
Added comment: Screened 216 patients with Idiopathic hypogonadotropic hypogonadism by exome sequencing. Identified 10 individuals from 7 families with heterozygous SEMA3F missense variants. In 4 of the kindreds, there was at least one more gene known to be associated with IHH (oligogenecity). Provide unequivocal human embryonic data showing the expression of SEMA3F along the developing human GnRH migratory pathway. SEMA3Fs harboring the P452T, T29M, and T724M missense variants showed impaired SEMA3F secretion in whole cell lysates.
Sources: Literature
Differences of Sex Development v0.207 PLXNA3 Chirag Patel gene: PLXNA3 was added
gene: PLXNA3 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: PLXNA3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PLXNA3 were set to PMID: 33495532
Phenotypes for gene: PLXNA3 were set to Hypogonadotropic hypogonadism
Added comment: Screened 216 patients with Idiopathic hypogonadotropic hypogonadism by exome sequencing. Identified 7 individuals from 5 families with hemizygous PLXNA3 missense variants.
In 2 of the kindreds, there was at least one more gene known to be associated with IHH (oligogenecity). Data provided with evidence that PLXNA3, a key component of the SEMA3F holoreceptor complex,31 is expressed by the human GnRH and olfactory/vomeronasal systems. S646P variant showed PLXNA3 localization exclusively in the ER, indicating that the variant S646P disrupts cell surface localization of PLXNA3.
Sources: Literature
Differences of Sex Development v0.206 LHCGR Zornitza Stark Marked gene: LHCGR as ready
Differences of Sex Development v0.206 LHCGR Zornitza Stark Gene: lhcgr has been classified as Green List (High Evidence).
Differences of Sex Development v0.206 LHCGR Zornitza Stark Phenotypes for gene: LHCGR were changed from to Luteinizing hormone resistance, female, (MIM#238320); Leydig cell hypoplasia with pseudohermaphroditism, (MIM#238320); Leydig cell hypoplasia with hypergonadotropic hypogonadism, (MIM#238320); Precocious puberty, male, (MIM#176410)
Differences of Sex Development v0.205 LHCGR Zornitza Stark Publications for gene: LHCGR were set to
Differences of Sex Development v0.204 LHCGR Zornitza Stark Mode of inheritance for gene: LHCGR was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.203 LHCGR Zornitza Stark reviewed gene: LHCGR: Rating: GREEN; Mode of pathogenicity: None; Publications: 11041448; Phenotypes: Luteinizing hormone resistance, female, (MIM#238320), Leydig cell hypoplasia with pseudohermaphroditism, (MIM#238320), Leydig cell hypoplasia with hypergonadotropic hypogonadism, (MIM#238320), Precocious puberty, male, (MIM#176410); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.203 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Differences of Sex Development v0.202 MKRN3 Zornitza Stark Tag SV/CNV tag was added to gene: MKRN3.
Tag 5'UTR tag was added to gene: MKRN3.
Differences of Sex Development v0.202 MKRN3 Zornitza Stark Phenotypes for gene: MKRN3 were changed from central precocious puberty to Precocious puberty, central, 2, MIM# 615346
Differences of Sex Development v0.201 MKRN3 Zornitza Stark Classified gene: MKRN3 as Green List (high evidence)
Differences of Sex Development v0.201 MKRN3 Zornitza Stark Gene: mkrn3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.200 DLK1 Zornitza Stark edited their review of gene: DLK1: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Differences of Sex Development v0.200 DLK1 Zornitza Stark Marked gene: DLK1 as ready
Differences of Sex Development v0.200 DLK1 Zornitza Stark Gene: dlk1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.200 DLK1 Zornitza Stark Phenotypes for gene: DLK1 were changed from to central precocious puberty
Differences of Sex Development v0.199 DLK1 Zornitza Stark Publications for gene: DLK1 were set to
Differences of Sex Development v0.198 DLK1 Zornitza Stark Classified gene: DLK1 as Green List (high evidence)
Differences of Sex Development v0.198 DLK1 Zornitza Stark Gene: dlk1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.197 DLK1 Zornitza Stark reviewed gene: DLK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28324015, 30462238; Phenotypes: central precocious puberty; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.197 MKRN3 Natasha Brown Marked gene: MKRN3 as ready
Differences of Sex Development v0.197 MKRN3 Natasha Brown Gene: mkrn3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.197 MKRN3 Natasha Brown changed review comment from: PMID: 31687022 4 novel missense, c.1138G > A (p.Glu380Lys), c.1420T > A (p.Leu474Met), c.673C > G (p.Leu225Val), and c.1071C > G (p.Ile357Met) in two sporadic cases and three familial cases. ACMG: (p.Glu380Lys and p.Ile357Met) = LP, but (p.Leu474Met) (p.Leu225Val) are VUS.
PMID: 31636607 3 novel promotor variants found in 6 unrelated females; significant reduction of MKRN3 promoter activity using luciferase assays.
PMID: 32480405 - 2 females with whole gene deletions of MKRN3
PMID: 31041429 systematic review/meta analysis: "Patients with MKRN3 mutations presented with signs and symptoms of early reactivation of the hypothalamic-pituitary-gonadal axis, represented by precocious development of sexual characteristics, BA advancement, and pubertal levels of basal or poststimulated LH"
Sources: Literature; to: PMID: 23738509: four (3fs; 1missense) novel heterozygous mutations in MKRN3, in 5 of the 15 families; both sexes were affected; mouse model confirms low expression.
PMID: 31687022 4 novel missense, c.1138G > A (p.Glu380Lys), c.1420T > A (p.Leu474Met), c.673C > G (p.Leu225Val), and c.1071C > G (p.Ile357Met) in two sporadic cases and three familial cases. ACMG: (p.Glu380Lys and p.Ile357Met) = LP, but (p.Leu474Met) (p.Leu225Val) are VUS.
PMID: 31636607 3 novel promotor variants found in 6 unrelated females; significant reduction of MKRN3 promoter activity using luciferase assays.
PMID: 32480405 - 2 females with whole gene deletions of MKRN3
PMID: 31041429 systematic review/meta analysis: "Patients with MKRN3 mutations presented with signs and symptoms of early reactivation of the hypothalamic-pituitary-gonadal axis, represented by precocious development of sexual characteristics, BA advancement, and pubertal levels of basal or poststimulated LH"
Sources: Literature
Differences of Sex Development v0.197 MKRN3 Natasha Brown gene: MKRN3 was added
gene: MKRN3 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: MKRN3 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: MKRN3 were set to PMID: 31687022; 31041429; 31636607; 32480405
Phenotypes for gene: MKRN3 were set to central precocious puberty
Penetrance for gene: MKRN3 were set to unknown
Review for gene: MKRN3 was set to GREEN
Added comment: PMID: 31687022 4 novel missense, c.1138G > A (p.Glu380Lys), c.1420T > A (p.Leu474Met), c.673C > G (p.Leu225Val), and c.1071C > G (p.Ile357Met) in two sporadic cases and three familial cases. ACMG: (p.Glu380Lys and p.Ile357Met) = LP, but (p.Leu474Met) (p.Leu225Val) are VUS.
PMID: 31636607 3 novel promotor variants found in 6 unrelated females; significant reduction of MKRN3 promoter activity using luciferase assays.
PMID: 32480405 - 2 females with whole gene deletions of MKRN3
PMID: 31041429 systematic review/meta analysis: "Patients with MKRN3 mutations presented with signs and symptoms of early reactivation of the hypothalamic-pituitary-gonadal axis, represented by precocious development of sexual characteristics, BA advancement, and pubertal levels of basal or poststimulated LH"
Sources: Literature
Differences of Sex Development v0.196 DLK1 Natasha Brown gene: DLK1 was added
gene: DLK1 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: DLK1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Penetrance for gene: DLK1 were set to unknown
Differences of Sex Development v0.195 CYP19A1 Zornitza Stark Marked gene: CYP19A1 as ready
Differences of Sex Development v0.195 CYP19A1 Zornitza Stark Gene: cyp19a1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.195 CYP19A1 Zornitza Stark Phenotypes for gene: CYP19A1 were changed from to Aromatase deficiency (MIM#613546), AR; Aromatase excess syndrome (MIM#139300), AD
Differences of Sex Development v0.194 CYP19A1 Zornitza Stark Publications for gene: CYP19A1 were set to
Differences of Sex Development v0.193 CYP19A1 Zornitza Stark Mode of inheritance for gene: CYP19A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.192 CYP19A1 Zornitza Stark Tag SV/CNV tag was added to gene: CYP19A1.
Differences of Sex Development v0.192 CYP19A1 Teresa Zhao reviewed gene: CYP19A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17164303, 25264451; Phenotypes: Aromatase deficiency (MIM#613546), AR, Aromatase excess syndrome (MIM#139300), AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.192 AMH Zornitza Stark Tag founder tag was added to gene: AMH.
Differences of Sex Development v0.192 AMH Seb Lunke Marked gene: AMH as ready
Differences of Sex Development v0.192 AMH Seb Lunke Added comment: Comment when marking as ready: 64 different alleles have been discovered in 79 families. There is a common 27-bp deletion in the kinase domain in caucasians.
Differences of Sex Development v0.192 AMH Seb Lunke Gene: amh has been classified as Green List (High Evidence).
Differences of Sex Development v0.192 AMH Seb Lunke Phenotypes for gene: AMH were changed from to Persistent Mullerian duct syndrome, type I (MIM#261550)
Differences of Sex Development v0.191 AMH Seb Lunke Publications for gene: AMH were set to
Differences of Sex Development v0.190 AMH Seb Lunke Mode of inheritance for gene: AMH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.189 AMH Teresa Zhao reviewed gene: AMH: Rating: GREEN; Mode of pathogenicity: None; Publications: 32172781; Phenotypes: Persistent Mullerian duct syndrome, type I (MIM#261550); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.189 PAX8 Zornitza Stark Marked gene: PAX8 as ready
Differences of Sex Development v0.189 PAX8 Zornitza Stark Gene: pax8 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.189 PAX8 Zornitza Stark Classified gene: PAX8 as Amber List (moderate evidence)
Differences of Sex Development v0.189 PAX8 Zornitza Stark Gene: pax8 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.188 PAX8 Zornitza Stark gene: PAX8 was added
gene: PAX8 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: PAX8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAX8 were set to 33434492
Phenotypes for gene: PAX8 were set to Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS)
Review for gene: PAX8 was set to AMBER
Added comment: 5 individuals identified in large cohorts with MRKHS and likely deleterious variants in PAX8. At least one of the individuals had congenital hypothyroidism together with features of MRKHS.

Variants in this gene are associated with congenital hypothyroidism.
Sources: Literature
Differences of Sex Development v0.187 BMP7 Zornitza Stark Marked gene: BMP7 as ready
Differences of Sex Development v0.187 BMP7 Zornitza Stark Gene: bmp7 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.187 BMP7 Zornitza Stark gene: BMP7 was added
gene: BMP7 was added to Differences of Sex Development. Sources: Literature
Mode of inheritance for gene: BMP7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP7 were set to 33434492
Phenotypes for gene: BMP7 were set to Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS)
Review for gene: BMP7 was set to RED
Added comment: Two individuals with likely deleterious variants identified in a cohort of individuals with MRKHS.
Sources: Literature
Differences of Sex Development v0.186 TSPYL1 Zornitza Stark Classified gene: TSPYL1 as Green List (high evidence)
Differences of Sex Development v0.186 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.185 TSPYL1 Zornitza Stark reviewed gene: TSPYL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15273283, 19463995, 22137496, 25449952, 16418600, 32885560, 33075815; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome (MIM#608800), sudden infant death-dysgenesis of the testes syndrome MONDO:0012124; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.185 POR Zornitza Stark Marked gene: POR as ready
Differences of Sex Development v0.185 POR Zornitza Stark Gene: por has been classified as Green List (High Evidence).
Differences of Sex Development v0.185 POR Zornitza Stark Phenotypes for gene: POR were changed from to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, MIM#201750; Disordered steroidogenesis due to cytochrome P450 oxidoreductase, MIM#613571
Differences of Sex Development v0.184 POR Zornitza Stark Publications for gene: POR were set to
Differences of Sex Development v0.183 POR Zornitza Stark Mode of inheritance for gene: POR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.182 POR Zornitza Stark reviewed gene: POR: Rating: GREEN; Mode of pathogenicity: None; Publications: 27068427; Phenotypes: Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, MIM#201750, Disordered steroidogenesis due to cytochrome P450 oxidoreductase, MIM#613571; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.182 BMP15 Zornitza Stark Marked gene: BMP15 as ready
Differences of Sex Development v0.182 BMP15 Zornitza Stark Gene: bmp15 has been classified as Green List (High Evidence).
Differences of Sex Development v0.182 BMP15 Zornitza Stark Phenotypes for gene: BMP15 were changed from to Ovarian dysgenesis 2, MIM# 300510; Premature ovarian failure 4, MIM# 300510
Differences of Sex Development v0.181 BMP15 Zornitza Stark Publications for gene: BMP15 were set to
Differences of Sex Development v0.180 BMP15 Zornitza Stark Mode of inheritance for gene: BMP15 was changed from Unknown to Other
Differences of Sex Development v0.179 BMP15 Zornitza Stark reviewed gene: BMP15: Rating: GREEN; Mode of pathogenicity: None; Publications: 15136966, 16508750, 16464940; Phenotypes: Ovarian dysgenesis 2, MIM# 300510, Premature ovarian failure 4, MIM# 300510; Mode of inheritance: Other
Differences of Sex Development v0.179 GATA4 Zornitza Stark Marked gene: GATA4 as ready
Differences of Sex Development v0.179 GATA4 Zornitza Stark Gene: gata4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.179 GATA4 Zornitza Stark Phenotypes for gene: GATA4 were changed from to Testicular anomalies with or without congenital heart disease, MIM# 615542
Differences of Sex Development v0.178 GATA4 Zornitza Stark Publications for gene: GATA4 were set to
Differences of Sex Development v0.177 GATA4 Zornitza Stark Mode of inheritance for gene: GATA4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.176 GATA4 Zornitza Stark Classified gene: GATA4 as Amber List (moderate evidence)
Differences of Sex Development v0.176 GATA4 Zornitza Stark Gene: gata4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.175 GATA4 Michelle Torres reviewed gene: GATA4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 21220346, 30455927, 29735817, 27899157, 26490186, 29670578, 32992319; Phenotypes: ?Testicular anomalies with or without congenital heart disease 615542 AD, Atrial septal defect 2 607941 AD, Atrioventricular septal defect 4 614430 AD, Tetralogy of Fallot 187500 AD, Ventricular septal defect 1 614429 AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.175 NR5A1 Zornitza Stark Marked gene: NR5A1 as ready
Differences of Sex Development v0.175 NR5A1 Zornitza Stark Gene: nr5a1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.175 NR5A1 Zornitza Stark Phenotypes for gene: NR5A1 were changed from to Adrenocortical insufficiency, (MIM#612964); 46, XX sex reversal 4, (MIM# 617480); Premature ovarian failure 7, (MIM#612964); Spermatogenic failure 8, (MIM#613957); 46XY sex reversal 3, (MIM#612965)
Differences of Sex Development v0.174 NR5A1 Zornitza Stark Publications for gene: NR5A1 were set to
Differences of Sex Development v0.173 NR5A1 Zornitza Stark Mode of inheritance for gene: NR5A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.172 NR5A1 Ain Roesley edited their review of gene: NR5A1: Added comment: 188 variants from 238 cases. No genotype-phenotype correlation establised; Changed phenotypes: Adrenocortical insufficiency, (MIM#612964), 46, XX sex reversal 4, (MIM# 617480), Premature ovarian failure 7, (MIM#612964), Spermatogenic failure 8, (MIM#613957), 46XY sex reversal 3, (MIM#612965)
Differences of Sex Development v0.172 NR5A1 Ain Roesley reviewed gene: NR5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31513305; Phenotypes: Adrenocortical insufficiency, (MIM#612964), 46, XX sex reversal 4, (MIM# 617480), Premature ovarian failure 7, (MIM#612964), Spermatogenic failure 8, (MIM#613957), 46XY sex reversal 3, (MIM#612965), Autosomal dominant; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.172 Tiong Tan Panel name changed from Disorders of Sex Differentiation to Differences of Sex Development
Differences of Sex Development v0.171 IGSF10 Zornitza Stark edited their review of gene: IGSF10: Changed rating: AMBER
Differences of Sex Development v0.171 IGSF10 Zornitza Stark Marked gene: IGSF10 as ready
Differences of Sex Development v0.171 IGSF10 Zornitza Stark Gene: igsf10 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.171 IGSF10 Zornitza Stark Classified gene: IGSF10 as Amber List (moderate evidence)
Differences of Sex Development v0.171 IGSF10 Zornitza Stark Gene: igsf10 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.170 IGSF10 Zornitza Stark gene: IGSF10 was added
gene: IGSF10 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: IGSF10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IGSF10 were set to 27137492; 31042289
Phenotypes for gene: IGSF10 were set to delayed puberty; hypogonadotropic hypogonadism; primary ovary insufficiency
Added comment: PMID: 27137492 - 4 Finnish families segregating p.Glu161Lys, but Finnish MAF in ExAC is 2%. Another six additional families with a possible missense, but variants are seen in ExAC suggesting incomplete penetrance. Supporting in vitro functional assays and zebrafish model. PMID: 31042289 - 2 unrelated consanguineous families with homozygous variants and family with a heterozygous frameshift and apparent incomplete penetrance.
Sources: Expert list
Differences of Sex Development v0.169 TCF12 Zornitza Stark Marked gene: TCF12 as ready
Differences of Sex Development v0.169 TCF12 Zornitza Stark Gene: tcf12 has been classified as Green List (High Evidence).
Differences of Sex Development v0.169 TCF12 Zornitza Stark Classified gene: TCF12 as Green List (high evidence)
Differences of Sex Development v0.169 TCF12 Zornitza Stark Gene: tcf12 has been classified as Green List (High Evidence).
Differences of Sex Development v0.168 TCF12 Zornitza Stark gene: TCF12 was added
gene: TCF12 was added to Disorders of Sex Differentiation. Sources: Literature
Mode of inheritance for gene: TCF12 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TCF12 were set to 32620954
Phenotypes for gene: TCF12 were set to Kallmann syndrome
Review for gene: TCF12 was set to GREEN
Added comment: Note monoallelic variants in this gene are a well-established cause of craniosynostosis.
------------------------------------------------------------------------------------------------------------------------

- PMID: 32620954 (2020) - 13 unrelated kindreds (11 de novo, 1 AD and 1 AR) comprising 14 affected individuals with an anosmic form of isolated GnRH deficiency (IGD) (Kallman syndrome) due to different LoF variants in TCF12.

Clinical manifestation included anosmia and pubertal failure (with reproductive phenotypes such as micropenis, bilateral cryptorchidism, hypospadias). Two unrelated individuals within the cohort additionally exhibited craniosynostosis, and a further two pedigrees had a family history of craniosynostosis (that did not affect the index case). Multiplex cases typically presented incomplete penetrance.

Loss of tcf12 in a mutant zebrafish model perturbed GnRH neuronal patterning, with concomitant expression attenuation of tcf3a/b and stub1 (latter mutated in other syndromic forms of IGD). Furthermore, restored STUB1 expression rescued loss of tcf12 in vivo.

Green for mono-allelic variants, caution with bi-allelic variants.
Sources: Literature
Differences of Sex Development v0.167 NR0B1 Zornitza Stark Marked gene: NR0B1 as ready
Differences of Sex Development v0.167 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.167 NR0B1 Zornitza Stark Phenotypes for gene: NR0B1 were changed from to 46XY sex reversal 2, dosage-sensitive, MIM# 300018
Differences of Sex Development v0.166 NR0B1 Zornitza Stark Publications for gene: NR0B1 were set to
Differences of Sex Development v0.165 NR0B1 Zornitza Stark Mode of inheritance for gene: NR0B1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.164 NR0B1 Zornitza Stark Classified gene: NR0B1 as Amber List (moderate evidence)
Differences of Sex Development v0.164 NR0B1 Zornitza Stark Gene: nr0b1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.163 NR0B1 Zornitza Stark Tag SV/CNV tag was added to gene: NR0B1.
Differences of Sex Development v0.163 NR0B1 Zornitza Stark reviewed gene: NR0B1: Rating: AMBER; Mode of pathogenicity: None; Publications: 7951319; Phenotypes: 46XY sex reversal 2, dosage-sensitive, MIM# 300018; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.161 HOXA13 Zornitza Stark Marked gene: HOXA13 as ready
Differences of Sex Development v0.161 HOXA13 Zornitza Stark Gene: hoxa13 has been classified as Green List (High Evidence).
Differences of Sex Development v0.161 PROKR2 Zornitza Stark Marked gene: PROKR2 as ready
Differences of Sex Development v0.161 PROKR2 Zornitza Stark Gene: prokr2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.161 PROKR2 Zornitza Stark Phenotypes for gene: PROKR2 were changed from to Hypogonadotropic hypogonadism 3 with or without anosmia, MIM# 244200
Differences of Sex Development v0.160 PROKR2 Zornitza Stark Publications for gene: PROKR2 were set to
Differences of Sex Development v0.159 PROKR2 Zornitza Stark Mode of inheritance for gene: PROKR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.157 NSMF Zornitza Stark Marked gene: NSMF as ready
Differences of Sex Development v0.157 NSMF Zornitza Stark Gene: nsmf has been classified as Red List (Low Evidence).
Differences of Sex Development v0.157 NSMF Zornitza Stark gene: NSMF was added
gene: NSMF was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: NSMF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSMF were set to 15362570; 17235395; 21700882
Phenotypes for gene: NSMF were set to Hypogonadotropic hypogonadism 9 with or without anosmia, MIM# 614838
Review for gene: NSMF was set to RED
Added comment: Rare variants reported in individuals with IHH; however, variants in other IHH genes also present, and at least one of the variants has a very high population frequency in gnomad (intronic 8-bp deletion ending 14 bp before exon 10 (1159-14_-22del), present in 258 individuals).
Sources: Expert list
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Tag disputed tag was added to gene: SPRY4.
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Marked gene: SPRY4 as ready
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Gene: spry4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Classified gene: SPRY4 as Amber List (moderate evidence)
Differences of Sex Development v0.156 SPRY4 Zornitza Stark Gene: spry4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.155 SPRY4 Zornitza Stark gene: SPRY4 was added
gene: SPRY4 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: SPRY4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPRY4 were set to 23643382
Phenotypes for gene: SPRY4 were set to Hypogonadotropic hypogonadism 17 with or without anosmia, MIM# 615266
Review for gene: SPRY4 was set to AMBER
Added comment: 14 unrelated individuals reported originally. Three of these had variants in other IHH genes. The p.Lys177Arg variant is present in 454 individuals in gnomad, p.Ser241Tyr is present in 1279 individuals including 6 homozygotes, p.Val304Ile is present in 457 individuals. These population frequencies cast doubt on the gene-disease relationship.
Sources: Expert list
Differences of Sex Development v0.154 KISS1 Zornitza Stark Marked gene: KISS1 as ready
Differences of Sex Development v0.154 KISS1 Zornitza Stark Gene: kiss1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.154 KISS1 Zornitza Stark Classified gene: KISS1 as Amber List (moderate evidence)
Differences of Sex Development v0.154 KISS1 Zornitza Stark Gene: kiss1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.153 KISS1 Zornitza Stark gene: KISS1 was added
gene: KISS1 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: KISS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KISS1 were set to 22335740; 25783047; 22766261; 17563351
Phenotypes for gene: KISS1 were set to Hypogonadotropic hypogonadism 13 with or without anosmia, MIM# 614842
Review for gene: KISS1 was set to AMBER
Added comment: Reported in Turkish families, supportive mouse model, but no variants identified in other cohorts. Role of KISS1 receptor much more established.
Sources: Expert list
Differences of Sex Development v0.152 TACR3 Zornitza Stark Marked gene: TACR3 as ready
Differences of Sex Development v0.152 TACR3 Zornitza Stark Gene: tacr3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.152 TACR3 Zornitza Stark Classified gene: TACR3 as Green List (high evidence)
Differences of Sex Development v0.152 TACR3 Zornitza Stark Gene: tacr3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.151 TACR3 Zornitza Stark gene: TACR3 was added
gene: TACR3 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: TACR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TACR3 were set to 20332248; 19079066
Phenotypes for gene: TACR3 were set to Hypogonadotropic hypogonadism 11 with or without anosmia, MIM# 614840
Review for gene: TACR3 was set to GREEN
Added comment: Multiple families reported.
Sources: Expert list
Differences of Sex Development v0.150 INSL3 Zornitza Stark Marked gene: INSL3 as ready
Differences of Sex Development v0.150 INSL3 Zornitza Stark Gene: insl3 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.150 INSL3 Zornitza Stark Phenotypes for gene: INSL3 were changed from to Cryptorchidism, MIM# 219050
Differences of Sex Development v0.149 INSL3 Zornitza Stark Publications for gene: INSL3 were set to
Differences of Sex Development v0.148 INSL3 Zornitza Stark Mode of inheritance for gene: INSL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.147 INSL3 Zornitza Stark Classified gene: INSL3 as Amber List (moderate evidence)
Differences of Sex Development v0.147 INSL3 Zornitza Stark Gene: insl3 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.146 INSL3 Zornitza Stark reviewed gene: INSL3: Rating: AMBER; Mode of pathogenicity: None; Publications: 12601553, 12970298, 11095425; Phenotypes: Cryptorchidism, MIM# 219050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.146 IL17RD Zornitza Stark Tag disputed tag was added to gene: IL17RD.
Differences of Sex Development v0.146 IL17RD Zornitza Stark Marked gene: IL17RD as ready
Differences of Sex Development v0.146 IL17RD Zornitza Stark Gene: il17rd has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.146 IL17RD Zornitza Stark Phenotypes for gene: IL17RD were changed from to Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267
Differences of Sex Development v0.145 IL17RD Zornitza Stark Publications for gene: IL17RD were set to
Differences of Sex Development v0.144 IL17RD Zornitza Stark Mode of inheritance for gene: IL17RD was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.143 IL17RD Zornitza Stark Classified gene: IL17RD as Amber List (moderate evidence)
Differences of Sex Development v0.143 IL17RD Zornitza Stark Gene: il17rd has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.142 IL17RD Zornitza Stark edited their review of gene: IL17RD: Changed rating: AMBER
Differences of Sex Development v0.142 IL17RD Zornitza Stark reviewed gene: IL17RD: Rating: GREEN; Mode of pathogenicity: None; Publications: 23643382, 32389901; Phenotypes: Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.142 HSD17B4 Zornitza Stark Marked gene: HSD17B4 as ready
Differences of Sex Development v0.142 HSD17B4 Zornitza Stark Gene: hsd17b4 has been classified as Green List (High Evidence).
Differences of Sex Development v0.142 HSD17B4 Zornitza Stark Phenotypes for gene: HSD17B4 were changed from to Perrault syndrome 1, MIM# 233400
Differences of Sex Development v0.141 HSD17B4 Zornitza Stark Publications for gene: HSD17B4 were set to
Differences of Sex Development v0.140 HSD17B4 Zornitza Stark Mode of inheritance for gene: HSD17B4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.139 HSD17B4 Zornitza Stark reviewed gene: HSD17B4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24553428, 23181892; Phenotypes: Perrault syndrome 1, MIM# 233400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.139 HS6ST1 Zornitza Stark Marked gene: HS6ST1 as ready
Differences of Sex Development v0.139 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.139 HS6ST1 Zornitza Stark Phenotypes for gene: HS6ST1 were changed from to {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880
Differences of Sex Development v0.138 HS6ST1 Zornitza Stark Publications for gene: HS6ST1 were set to
Differences of Sex Development v0.137 HS6ST1 Zornitza Stark Mode of inheritance for gene: HS6ST1 was changed from Unknown to Other
Differences of Sex Development v0.136 HS6ST1 Zornitza Stark Classified gene: HS6ST1 as Red List (low evidence)
Differences of Sex Development v0.136 HS6ST1 Zornitza Stark Gene: hs6st1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.135 HS6ST1 Zornitza Stark reviewed gene: HS6ST1: Rating: RED; Mode of pathogenicity: None; Publications: 21700882; Phenotypes: {Hypogonadotropic hypogonadism 15 with or without anosmia} 614880; Mode of inheritance: Other
Differences of Sex Development v0.135 HOXA13 Zornitza Stark Phenotypes for gene: HOXA13 were changed from to Hand-foot-uterus syndrome, MIM# 140000
Differences of Sex Development v0.134 HOXA13 Zornitza Stark Publications for gene: HOXA13 were set to
Differences of Sex Development v0.133 HOXA13 Zornitza Stark Mode of inheritance for gene: HOXA13 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.132 HOXA13 Zornitza Stark reviewed gene: HOXA13: Rating: GREEN; Mode of pathogenicity: None; Publications: 10839976, 9020844; Phenotypes: Hand-foot-uterus syndrome, MIM# 140000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.132 HESX1 Zornitza Stark Marked gene: HESX1 as ready
Differences of Sex Development v0.132 HESX1 Zornitza Stark Gene: hesx1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.132 HESX1 Zornitza Stark Phenotypes for gene: HESX1 were changed from to Pituitary hormone deficiency, combined, 5, MIM# 182230
Differences of Sex Development v0.131 HESX1 Zornitza Stark Mode of inheritance for gene: HESX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.130 HESX1 Zornitza Stark reviewed gene: HESX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined, 5, MIM# 182230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.130 GNRH1 Zornitza Stark Marked gene: GNRH1 as ready
Differences of Sex Development v0.130 GNRH1 Zornitza Stark Gene: gnrh1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.130 GNRH1 Zornitza Stark Phenotypes for gene: GNRH1 were changed from to Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841
Differences of Sex Development v0.129 GNRH1 Zornitza Stark Publications for gene: GNRH1 were set to
Differences of Sex Development v0.128 GNRH1 Zornitza Stark Mode of inheritance for gene: GNRH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.127 GNRH1 Zornitza Stark reviewed gene: GNRH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19535795, 19567835, 32134721, 31200363, 26595427; Phenotypes: Hypogonadotropic hypogonadism 12 with or without anosmia, MIM# 614841; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.127 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Differences of Sex Development v0.126 TSPYL1 Zornitza Stark Tag disputed tag was added to gene: TSPYL1.
Differences of Sex Development v0.126 TSPYL1 Zornitza Stark Classified gene: TSPYL1 as Amber List (moderate evidence)
Differences of Sex Development v0.126 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.125 TSPYL1 Zornitza Stark Marked gene: TSPYL1 as ready
Differences of Sex Development v0.125 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.125 TSPYL1 Zornitza Stark Phenotypes for gene: TSPYL1 were changed from to Sudden infant death with dysgenesis of the testes syndrome (MIM#608800)
Differences of Sex Development v0.124 TSPYL1 Zornitza Stark Publications for gene: TSPYL1 were set to
Differences of Sex Development v0.123 TSPYL1 Zornitza Stark Mode of inheritance for gene: TSPYL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.122 TSPYL1 Zornitza Stark Classified gene: TSPYL1 as Red List (low evidence)
Differences of Sex Development v0.122 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.121 WDR11 Zornitza Stark Marked gene: WDR11 as ready
Differences of Sex Development v0.121 WDR11 Zornitza Stark Gene: wdr11 has been classified as Green List (High Evidence).
Differences of Sex Development v0.121 WDR11 Zornitza Stark Phenotypes for gene: WDR11 were changed from to Hypogonadotropic hypogonadism 14 with or without anosmia, MIM#614858
Differences of Sex Development v0.120 WDR11 Zornitza Stark Publications for gene: WDR11 were set to
Differences of Sex Development v0.119 WDR11 Zornitza Stark Mode of inheritance for gene: WDR11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.118 KISS1R Zornitza Stark Marked gene: KISS1R as ready
Differences of Sex Development v0.118 KISS1R Zornitza Stark Gene: kiss1r has been classified as Green List (High Evidence).
Differences of Sex Development v0.118 KISS1R Zornitza Stark Phenotypes for gene: KISS1R were changed from to Hypogonadotropic hypogonadism 8 with or without anosmia (MIM#614837)
Differences of Sex Development v0.117 KISS1R Zornitza Stark Publications for gene: KISS1R were set to
Differences of Sex Development v0.116 KISS1R Zornitza Stark Mode of inheritance for gene: KISS1R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.115 LEP Zornitza Stark Marked gene: LEP as ready
Differences of Sex Development v0.115 LEP Zornitza Stark Gene: lep has been classified as Green List (High Evidence).
Differences of Sex Development v0.115 LEP Zornitza Stark Phenotypes for gene: LEP were changed from Obesity, morbid, due to leptin deficiency (MIM#614962) to Obesity, morbid, due to leptin deficiency (MIM#614962)
Differences of Sex Development v0.115 LEP Zornitza Stark Phenotypes for gene: LEP were changed from to Obesity, morbid, due to leptin deficiency (MIM#614962)
Differences of Sex Development v0.114 LEP Zornitza Stark Publications for gene: LEP were set to
Differences of Sex Development v0.113 LEP Zornitza Stark Mode of inheritance for gene: LEP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.112 LEPR Zornitza Stark Marked gene: LEPR as ready
Differences of Sex Development v0.112 LEPR Zornitza Stark Gene: lepr has been classified as Green List (High Evidence).
Differences of Sex Development v0.112 LEPR Zornitza Stark Phenotypes for gene: LEPR were changed from to Obesity, morbid, due to leptin receptor deficiency (MIM#614963)
Differences of Sex Development v0.111 LEPR Zornitza Stark Publications for gene: LEPR were set to
Differences of Sex Development v0.110 LEPR Zornitza Stark Mode of inheritance for gene: LEPR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.109 FGF17 Zornitza Stark Marked gene: FGF17 as ready
Differences of Sex Development v0.109 FGF17 Zornitza Stark Added comment: Comment when marking as ready: Borderline Green/Amber: contribution may not be monogenic.
Differences of Sex Development v0.109 FGF17 Zornitza Stark Gene: fgf17 has been classified as Green List (High Evidence).
Differences of Sex Development v0.109 FGF17 Zornitza Stark Publications for gene: FGF17 were set to
Differences of Sex Development v0.108 FGF17 Zornitza Stark Mode of inheritance for gene: FGF17 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.107 FGF17 Zornitza Stark reviewed gene: FGF17: Rating: GREEN; Mode of pathogenicity: None; Publications: 23643382, 31748124; Phenotypes: Hypogonadotropic hypogonadism 20 with or without anosmia, MIM# 615270; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.107 LHB Zornitza Stark Marked gene: LHB as ready
Differences of Sex Development v0.107 LHB Zornitza Stark Gene: lhb has been classified as Green List (High Evidence).
Differences of Sex Development v0.107 LHB Zornitza Stark Phenotypes for gene: LHB were changed from to Hypogonadotropic hypogonadism 23 with or without anosmia (MIM#228300)
Differences of Sex Development v0.106 LHB Zornitza Stark Publications for gene: LHB were set to
Differences of Sex Development v0.105 LHB Zornitza Stark Mode of inheritance for gene: LHB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.104 FEZF1 Zornitza Stark Marked gene: FEZF1 as ready
Differences of Sex Development v0.104 FEZF1 Zornitza Stark Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.104 FEZF1 Zornitza Stark Phenotypes for gene: FEZF1 were changed from to Hypogonadotropic hypogonadism 22, with or without anosmia 616030
Differences of Sex Development v0.103 FEZF1 Zornitza Stark Publications for gene: FEZF1 were set to
Differences of Sex Development v0.102 FEZF1 Zornitza Stark Mode of inheritance for gene: FEZF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.101 FEZF1 Zornitza Stark Classified gene: FEZF1 as Amber List (moderate evidence)
Differences of Sex Development v0.101 FEZF1 Zornitza Stark Gene: fezf1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.100 ESR2 Zornitza Stark Marked gene: ESR2 as ready
Differences of Sex Development v0.100 ESR2 Zornitza Stark Gene: esr2 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.100 ESR2 Zornitza Stark Phenotypes for gene: ESR2 were changed from 46,XY Disorders of Sex Development to 46,XY Disorders of Sex Development; Ovarian dysgenesis 8, MIM# 618187
Differences of Sex Development v0.99 ESR2 Zornitza Stark Publications for gene: ESR2 were set to 29261182; 9861029
Differences of Sex Development v0.98 ESR2 Zornitza Stark Classified gene: ESR2 as Amber List (moderate evidence)
Differences of Sex Development v0.98 ESR2 Zornitza Stark Gene: esr2 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.97 ESR2 Zornitza Stark reviewed gene: ESR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30113650; Phenotypes: Ovarian dysgenesis 8, MIM# 618187; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.97 ERAL1 Zornitza Stark Marked gene: ERAL1 as ready
Differences of Sex Development v0.97 ERAL1 Zornitza Stark Gene: eral1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.97 ERAL1 Zornitza Stark Classified gene: ERAL1 as Red List (low evidence)
Differences of Sex Development v0.97 ERAL1 Zornitza Stark Gene: eral1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.96 ERAL1 Zornitza Stark reviewed gene: ERAL1: Rating: RED; Mode of pathogenicity: None; Publications: 28449065; Phenotypes: Perrault syndrome 6, MIM# 617565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.96 MKKS Zornitza Stark reviewed gene: MKKS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 6 (MIM#605231), McKusick-Kaufman syndrome (MIM#236700); Mode of inheritance: None
Differences of Sex Development v0.96 MKKS Zornitza Stark Marked gene: MKKS as ready
Differences of Sex Development v0.96 MKKS Zornitza Stark Gene: mkks has been classified as Red List (Low Evidence).
Differences of Sex Development v0.96 MKKS Zornitza Stark Phenotypes for gene: MKKS were changed from to Bardet-Biedl syndrome 6 (MIM#605231); McKusick-Kaufman syndrome (MIM#236700)
Differences of Sex Development v0.95 MKKS Zornitza Stark Publications for gene: MKKS were set to
Differences of Sex Development v0.94 MKKS Zornitza Stark Mode of inheritance for gene: MKKS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.93 MKKS Zornitza Stark Classified gene: MKKS as Red List (low evidence)
Differences of Sex Development v0.93 MKKS Zornitza Stark Gene: mkks has been classified as Red List (Low Evidence).
Differences of Sex Development v0.92 KISS1R Crystle Lee reviewed gene: KISS1R: Rating: GREEN; Mode of pathogenicity: None; Publications: 17164310, 31073722, 14573733; Phenotypes: Hypogonadotropic hypogonadism 8 with or without anosmia (MIM#614837); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.92 LEP Crystle Lee reviewed gene: LEP: Rating: GREEN; Mode of pathogenicity: None; Publications: 26567097, 31483094; Phenotypes: Obesity, morbid, due to leptin deficiency (MIM#614962); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.92 DMRT1 Zornitza Stark Marked gene: DMRT1 as ready
Differences of Sex Development v0.92 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.92 DMRT1 Zornitza Stark Classified gene: DMRT1 as Red List (low evidence)
Differences of Sex Development v0.92 DMRT1 Zornitza Stark Gene: dmrt1 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.91 DHCR24 Zornitza Stark Marked gene: DHCR24 as ready
Differences of Sex Development v0.91 DHCR24 Zornitza Stark Gene: dhcr24 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.91 DHCR24 Zornitza Stark Phenotypes for gene: DHCR24 were changed from to Desmosterolosis, MIM# 602398
Differences of Sex Development v0.90 DHCR24 Zornitza Stark Publications for gene: DHCR24 were set to
Differences of Sex Development v0.89 DHCR24 Zornitza Stark Mode of inheritance for gene: DHCR24 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.88 DHCR24 Zornitza Stark Classified gene: DHCR24 as Red List (low evidence)
Differences of Sex Development v0.88 DHCR24 Zornitza Stark Gene: dhcr24 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.87 CYB5A Zornitza Stark Marked gene: CYB5A as ready
Differences of Sex Development v0.87 CYB5A Zornitza Stark Gene: cyb5a has been classified as Green List (High Evidence).
Differences of Sex Development v0.87 CYB5A Zornitza Stark Phenotypes for gene: CYB5A were changed from Methemoglobinemia and ambiguous genitalia 250790 to Methemoglobinemia and ambiguous genitalia, MIM# 250790
Differences of Sex Development v0.86 CYB5A Zornitza Stark Classified gene: CYB5A as Green List (high evidence)
Differences of Sex Development v0.86 CYB5A Zornitza Stark Gene: cyb5a has been classified as Green List (High Evidence).
Differences of Sex Development v0.85 LHX3 Zornitza Stark Marked gene: LHX3 as ready
Differences of Sex Development v0.85 LHX3 Zornitza Stark Gene: lhx3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.85 LHX3 Zornitza Stark Mode of inheritance for gene: LHX3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.84 LHX3 Zornitza Stark Phenotypes for gene: LHX3 were changed from to Pituitary hormone deficiency, combined, 3 (MIM#221750)
Differences of Sex Development v0.83 LHX3 Zornitza Stark Publications for gene: LHX3 were set to
Differences of Sex Development v0.82 CUL4B Zornitza Stark Marked gene: CUL4B as ready
Differences of Sex Development v0.82 CUL4B Zornitza Stark Gene: cul4b has been classified as Green List (High Evidence).
Differences of Sex Development v0.82 CUL4B Zornitza Stark Mode of inheritance for gene: CUL4B was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.81 CUL4B Zornitza Stark Classified gene: CUL4B as Green List (high evidence)
Differences of Sex Development v0.81 CUL4B Zornitza Stark Gene: cul4b has been classified as Green List (High Evidence).
Differences of Sex Development v0.80 CBX2 Zornitza Stark Marked gene: CBX2 as ready
Differences of Sex Development v0.80 CBX2 Zornitza Stark Gene: cbx2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.80 CBX2 Zornitza Stark Phenotypes for gene: CBX2 were changed from to 46XY sex reversal 5, MIM# 613080
Differences of Sex Development v0.79 CBX2 Zornitza Stark Mode of inheritance for gene: CBX2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.78 CBX2 Zornitza Stark Publications for gene: CBX2 were set to
Differences of Sex Development v0.77 CBX2 Zornitza Stark Classified gene: CBX2 as Red List (low evidence)
Differences of Sex Development v0.77 CBX2 Zornitza Stark Gene: cbx2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.76 LEPR Crystle Lee reviewed gene: LEPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 17229951, 29545012; Phenotypes: Obesity, morbid, due to leptin receptor deficiency (MIM#614963); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.76 CBX2 Zornitza Stark reviewed gene: CBX2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: 46XY sex reversal 5, MIM# 613080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.76 MCM5 Zornitza Stark Marked gene: MCM5 as ready
Differences of Sex Development v0.76 MCM5 Zornitza Stark Gene: mcm5 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.76 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from Meier-Gorlin syndrome 8 (MIM#617564) to Meier-Gorlin syndrome 8 (MIM#617564)
Differences of Sex Development v0.75 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from Meier-Gorlin syndrome 8 (MIM#617564) to Meier-Gorlin syndrome 8 (MIM#617564)
Differences of Sex Development v0.75 MCM5 Zornitza Stark Phenotypes for gene: MCM5 were changed from ?Meier-Gorlin syndrome 8 (MIM#617564) to Meier-Gorlin syndrome 8 (MIM#617564)
Differences of Sex Development v0.74 MCM5 Zornitza Stark Classified gene: MCM5 as Red List (low evidence)
Differences of Sex Development v0.74 MCM5 Zornitza Stark Gene: mcm5 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.73 ATF3 Zornitza Stark Marked gene: ATF3 as ready
Differences of Sex Development v0.73 ATF3 Zornitza Stark Gene: atf3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.73 ATF3 Zornitza Stark Classified gene: ATF3 as Red List (low evidence)
Differences of Sex Development v0.73 ATF3 Zornitza Stark Gene: atf3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.72 LHB Crystle Lee reviewed gene: LHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 17761593, 28092701, 29476300, 22723313, 15602022; Phenotypes: Hypogonadotropic hypogonadism 23 with or without anosmia (MIM#228300); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.72 FEZF1 Elena Savva reviewed gene: FEZF1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 25192046, 32400067; Phenotypes: Hypogonadotropic hypogonadism 22, with or without anosmia 616030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.72 ERAL1 Elena Savva gene: ERAL1 was added
gene: ERAL1 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: ERAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERAL1 were set to PMID: 28449065
Phenotypes for gene: ERAL1 were set to Perrault syndrome 6 617565
Review for gene: ERAL1 was set to AMBER
Added comment: PMID: 28449065 - 3 unrelated patient with perrault syndrome with the same founder missense (p.Asn236Ile). Symptoms included hearing loss, premature ovarian failure, primary amenorrhea
Supported by functional analysis on patient cells, and transfected yeast reciprocating the phenotype.
Sources: Expert list
Differences of Sex Development v0.72 DMRT1 Elena Savva gene: DMRT1 was added
gene: DMRT1 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: DMRT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DMRT1 were set to PMID: 31479588; 24934491; 29527098
Phenotypes for gene: DMRT1 were set to Azoospermia
Review for gene: DMRT1 was set to RED
Added comment: PMID: 31479588 - 1 patient with azoospermia and XY genotype. Also carries an additional variant in KLHL10

PMID: 24934491 - 6 patients with male infertility, however the 4 identified variants were also found in 2 controls and have a high frequency in the population (gnomAD). No functional studies.

PMID: 23555275 - Identifies CNVs in azoospermia patients, calls the gene a risk factor
Sources: Expert list
Differences of Sex Development v0.72 DHCR24 Elena Savva reviewed gene: DHCR24: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 9450875, 11519011; Phenotypes: Desmosterolosis 602398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.72 CYB5A Elena Savva gene: CYB5A was added
gene: CYB5A was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: CYB5A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYB5A were set to PMID: 22170710; 32051920
Phenotypes for gene: CYB5A were set to Methemoglobinemia and ambiguous genitalia 250790
Review for gene: CYB5A was set to GREEN
Added comment: PMID: 22170710 - 3 siblings with 46,XY DSD, sex steroid deficiency, female genitalia and a homozygous missense variant. Supported by LOF functional studies. Mineralocorticoids and glucocorticoids were normal.

PMID: 32051920 - 1 female with a homozygous missense, no DSD but methemoglobinemia. All female genitalia are normal and she has had a normal female child.
Paper reviews prior reports and notes an additional 2 unrelated homozygous reports of 46 XY DSD patients with normal Methemoglobin. All variants were rare/absent (gnomAD) and PTCs.
Sources: Expert list
Differences of Sex Development v0.72 LHX3 Crystle Lee reviewed gene: LHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28302169, 17327381, 30262920; Phenotypes: Pituitary hormone deficiency, combined, 3 (MIM#221750); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.72 CUL4B Elena Savva gene: CUL4B was added
gene: CUL4B was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: CUL4B was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: CUL4B were set to PMID: 25385192
Phenotypes for gene: CUL4B were set to Mental retardation, X-linked, syndromic 15 (Cabezas type) 300354
Review for gene: CUL4B was set to GREEN
Added comment: PMID: 25385192 - 25 patients (11 families) with syndromic features including hypogonadism (85%) and gynecomastia (33%)
Sources: Expert list
Differences of Sex Development v0.72 NR3C1 Zornitza Stark Marked gene: NR3C1 as ready
Differences of Sex Development v0.72 NR3C1 Zornitza Stark Gene: nr3c1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.72 NR3C1 Zornitza Stark Phenotypes for gene: NR3C1 were changed from to Glucocorticoid resistance (MIM#615962)
Differences of Sex Development v0.71 NR3C1 Zornitza Stark Publications for gene: NR3C1 were set to
Differences of Sex Development v0.70 NR3C1 Zornitza Stark Mode of inheritance for gene: NR3C1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.69 CBX2 Elena Savva reviewed gene: CBX2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 19361780, 31719618, 23219007; Phenotypes: ?46XY sex reversal 5 613080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.69 MCM5 Crystle Lee gene: MCM5 was added
gene: MCM5 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: MCM5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM5 were set to 28198391
Phenotypes for gene: MCM5 were set to ?Meier-Gorlin syndrome 8 (MIM#617564)
Review for gene: MCM5 was set to RED
Added comment: Only single patient reported in 2017. Patient presented with microstomia, thick lips, micrognathia, bilateral microtia, low set ears and bilateral cryptorchidism.
Sources: Expert Review
Differences of Sex Development v0.69 MKKS Crystle Lee reviewed gene: MKKS: Rating: AMBER; Mode of pathogenicity: None; Publications: 10973251, 26900326, 10973238; Phenotypes: Bardet-Biedl syndrome 6 (MIM#605231), McKusick-Kaufman syndrome (MIM#236700); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.69 ATF3 Elena Savva reviewed gene: ATF3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Differences of Sex Development v0.69 NR3C1 Crystle Lee reviewed gene: NR3C1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30158362; Phenotypes: Glucocorticoid resistance (MIM#615962); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Differences of Sex Development v0.69 PCSK1 Zornitza Stark reviewed gene: PCSK1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Obesity with impaired prohormone processing (MIM#600955); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.69 PCSK1 Zornitza Stark Marked gene: PCSK1 as ready
Differences of Sex Development v0.69 PCSK1 Zornitza Stark Gene: pcsk1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.69 PCSK1 Zornitza Stark Phenotypes for gene: PCSK1 were changed from to Obesity with impaired prohormone processing (MIM#600955)
Differences of Sex Development v0.68 PCSK1 Zornitza Stark Publications for gene: PCSK1 were set to
Differences of Sex Development v0.67 PCSK1 Zornitza Stark Classified gene: PCSK1 as Amber List (moderate evidence)
Differences of Sex Development v0.67 PCSK1 Zornitza Stark Gene: pcsk1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.66 PROK2 Zornitza Stark Marked gene: PROK2 as ready
Differences of Sex Development v0.66 PROK2 Zornitza Stark Added comment: Comment when marking as ready: Evidence supporting association between bi-allelic variants causing IHH is stronger than for mono-allelic disease.
Differences of Sex Development v0.66 PROK2 Zornitza Stark Gene: prok2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.66 PROK2 Zornitza Stark Phenotypes for gene: PROK2 were changed from to Hypogonadotropic hypogonadism 4 with or without anosmia (MIM#610628)
Differences of Sex Development v0.65 PROK2 Zornitza Stark Publications for gene: PROK2 were set to
Differences of Sex Development v0.64 PROK2 Zornitza Stark Mode of inheritance for gene: PROK2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.63 PROP1 Zornitza Stark Marked gene: PROP1 as ready
Differences of Sex Development v0.63 PROP1 Zornitza Stark Gene: prop1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.63 PROP1 Zornitza Stark Phenotypes for gene: PROP1 were changed from to Pituitary hormone deficiency, combined, 2 (MIM#262600)
Differences of Sex Development v0.62 PROP1 Zornitza Stark Publications for gene: PROP1 were set to
Differences of Sex Development v0.61 PROP1 Zornitza Stark Mode of inheritance for gene: PROP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.60 RPL10 Zornitza Stark Marked gene: RPL10 as ready
Differences of Sex Development v0.60 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Differences of Sex Development v0.60 RPL10 Zornitza Stark Classified gene: RPL10 as Green List (high evidence)
Differences of Sex Development v0.60 RPL10 Zornitza Stark Gene: rpl10 has been classified as Green List (High Evidence).
Differences of Sex Development v0.59 SAMD9 Zornitza Stark Marked gene: SAMD9 as ready
Differences of Sex Development v0.59 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
Differences of Sex Development v0.59 SAMD9 Zornitza Stark Classified gene: SAMD9 as Green List (high evidence)
Differences of Sex Development v0.59 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
Differences of Sex Development v0.58 SEMA3E Zornitza Stark Marked gene: SEMA3E as ready
Differences of Sex Development v0.58 SEMA3E Zornitza Stark Gene: sema3e has been classified as Red List (Low Evidence).
Differences of Sex Development v0.58 SEMA3E Zornitza Stark Classified gene: SEMA3E as Red List (low evidence)
Differences of Sex Development v0.58 SEMA3E Zornitza Stark Gene: sema3e has been classified as Red List (Low Evidence).
Differences of Sex Development v0.57 SGPL1 Zornitza Stark Marked gene: SGPL1 as ready
Differences of Sex Development v0.57 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.57 SGPL1 Zornitza Stark Classified gene: SGPL1 as Green List (high evidence)
Differences of Sex Development v0.57 SGPL1 Zornitza Stark Gene: sgpl1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.56 SOX10 Zornitza Stark Marked gene: SOX10 as ready
Differences of Sex Development v0.56 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Differences of Sex Development v0.56 SOX10 Zornitza Stark Phenotypes for gene: SOX10 were changed from PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266) to Kallman syndrome; PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266)
Differences of Sex Development v0.55 SOX10 Zornitza Stark Classified gene: SOX10 as Green List (high evidence)
Differences of Sex Development v0.55 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Differences of Sex Development v0.54 TAC3 Zornitza Stark Marked gene: TAC3 as ready
Differences of Sex Development v0.54 TAC3 Zornitza Stark Gene: tac3 has been classified as Green List (High Evidence).
Differences of Sex Development v0.54 TAC3 Zornitza Stark Phenotypes for gene: TAC3 were changed from to Hypogonadotropic hypogonadism 10 with or without anosmia (MIM#614839)
Differences of Sex Development v0.53 TAC3 Zornitza Stark Publications for gene: TAC3 were set to
Differences of Sex Development v0.52 TAC3 Zornitza Stark Mode of inheritance for gene: TAC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.51 TOE1 Zornitza Stark Marked gene: TOE1 as ready
Differences of Sex Development v0.51 TOE1 Zornitza Stark Gene: toe1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.51 TOE1 Zornitza Stark Classified gene: TOE1 as Green List (high evidence)
Differences of Sex Development v0.51 TOE1 Zornitza Stark Gene: toe1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.50 PCSK1 Crystle Lee reviewed gene: PCSK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23562752, 23800642, 17595246, 25272002, 27187081; Phenotypes: Obesity with impaired prohormone processing (MIM#600955); Mode of inheritance: None
Differences of Sex Development v0.50 PROK2 Crystle Lee reviewed gene: PROK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18559922, 17054399, 17959774, 18285834; Phenotypes: Hypogonadotropic hypogonadism 4 with or without anosmia (MIM#610628); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.50 PROP1 Crystle Lee reviewed gene: PROP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15941866, 11549703; Phenotypes: Pituitary hormone deficiency, combined, 2 (MIM#262600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.50 AKR1C4 Zornitza Stark Marked gene: AKR1C4 as ready
Differences of Sex Development v0.50 AKR1C4 Zornitza Stark Gene: akr1c4 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.50 AKR1C4 Zornitza Stark Phenotypes for gene: AKR1C4 were changed from to {46XY sex reversal 8, modifier of}, MIM# 614279
Differences of Sex Development v0.49 AKR1C4 Zornitza Stark Publications for gene: AKR1C4 were set to
Differences of Sex Development v0.48 AKR1C4 Zornitza Stark Mode of inheritance for gene: AKR1C4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.47 AKR1C4 Zornitza Stark Classified gene: AKR1C4 as Red List (low evidence)
Differences of Sex Development v0.47 AKR1C4 Zornitza Stark Gene: akr1c4 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.46 AKR1C4 Zornitza Stark reviewed gene: AKR1C4: Rating: RED; Mode of pathogenicity: None; Publications: 21802064; Phenotypes: {46XY sex reversal 8, modifier of}, MIM# 614279; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.46 AKR1C2 Zornitza Stark Marked gene: AKR1C2 as ready
Differences of Sex Development v0.46 AKR1C2 Zornitza Stark Gene: akr1c2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.46 AKR1C2 Zornitza Stark Phenotypes for gene: AKR1C2 were changed from to 46XY sex reversal 8, MIM# 614279
Differences of Sex Development v0.45 AKR1C2 Zornitza Stark Publications for gene: AKR1C2 were set to
Differences of Sex Development v0.44 AKR1C2 Zornitza Stark Mode of inheritance for gene: AKR1C2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.43 AKR1C2 Zornitza Stark Classified gene: AKR1C2 as Red List (low evidence)
Differences of Sex Development v0.43 AKR1C2 Zornitza Stark Gene: akr1c2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.42 AKR1C2 Zornitza Stark reviewed gene: AKR1C2: Rating: RED; Mode of pathogenicity: None; Publications: 21802064; Phenotypes: 46XY sex reversal 8, MIM# 614279; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.42 RPL10 Crystle Lee gene: RPL10 was added
gene: RPL10 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: RPL10 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RPL10 were set to 25316788; 26290468; 25846674; 29066376
Phenotypes for gene: RPL10 were set to Mental retardation, X-linked, syndromic, 35 (MIM#300998)
Review for gene: RPL10 was set to GREEN
Added comment: At least 3 variants have been reported. Urogenital anomalies are a feature of the associated condition.

PMID: 25316788: Variant reported in 3 members of a family. Genitourinary abnormalities (ie cryptorchidism) reported in all 3 affected individuals.

PMID: 26290468: Reported in a family with two affected cousins presenting with X-linked ID, cerebellar hypoplasia, and spondylo-epiphyseal dysplasia. Only one of the affected males presented with cryptorchidism.

PMID: 25846674: 3 of 4 affected males in the family presented with urogenital anomalies
Sources: Expert Review
Differences of Sex Development v0.42 SAMD9 Crystle Lee gene: SAMD9 was added
gene: SAMD9 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: SAMD9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SAMD9 were set to 27182967
Phenotypes for gene: SAMD9 were set to MIRAGE syndrome (MIM#617053)
Review for gene: SAMD9 was set to GREEN
Added comment: At least 10 families ( 8 diff variants) reported in one publication. External genital abnormalities observed in all 46, XY patients.
Sources: Expert Review
Differences of Sex Development v0.42 SEMA3E Crystle Lee gene: SEMA3E was added
gene: SEMA3E was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: SEMA3E was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEMA3E were set to 25985275
Phenotypes for gene: SEMA3E were set to ?CHARGE syndrome (MIM#214800)
Review for gene: SEMA3E was set to RED
Added comment: Only one variant reported in 2 sibling with Kallman syndrome. Mouse model supports involvement of this gene with the phenotype. Variant not present in gnomad in homozygosity.
Sources: Expert Review
Differences of Sex Development v0.42 SGPL1 Crystle Lee gene: SGPL1 was added
gene: SGPL1 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: SGPL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGPL1 were set to 28165339; 28165343; 28181337
Phenotypes for gene: SGPL1 were set to Nephrotic syndrome, type 14 (MIM#617575)
Review for gene: SGPL1 was set to GREEN
Added comment: >5 families reported. Cryptorchidism and hypogonadism are features of the associated phenotype.
Sources: Expert Review
Differences of Sex Development v0.42 SOX10 Crystle Lee gene: SOX10 was added
gene: SOX10 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: SOX10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SOX10 were set to 23643381; 15004559
Phenotypes for gene: SOX10 were set to PCWH syndrome (MIM#609136); Waardenburg syndrome, type 2E, with or without neurologic involvement (MIM#611584); Waardenburg syndrome, type 4C (MIM#613266)
Mode of pathogenicity for gene: SOX10 was set to Other
Review for gene: SOX10 was set to GREEN
Added comment: Well reported gene disease association. Cryptorchidism and hypogonadism is a feature of Kallman Syndrome and WS4C

PMID: 23643381: Reported 6 variants in individuals with Kallman syndrome which is associated with hypogonadotropic hypogonadism. Functional studies performed.

PMID: 15004559: PCWH is caused by dominant-negative mutations (truncating variants) whereas NMD and thus haploinsufficiency results in WS4C
Sources: Expert Review
Differences of Sex Development v0.42 TAC3 Crystle Lee reviewed gene: TAC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 19079066, 20332248, 23329188, 22031817; Phenotypes: Hypogonadotropic hypogonadism 10 with or without anosmia (MIM#614839); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.42 TOE1 Crystle Lee gene: TOE1 was added
gene: TOE1 was added to Disorders of Sex Differentiation. Sources: Expert Review
Mode of inheritance for gene: TOE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOE1 were set to 28092684
Phenotypes for gene: TOE1 were set to Pontocerebellar hypoplasia, type 7 (MIM#614969)
Review for gene: TOE1 was set to GREEN
Added comment: >10 families with pontocerebellar hypoplasia type 7 (PCH7) reported with biallelic variants.MRI showed reduced cerebellar volume in these families. Ambiguous genitalia is a feature of this condition.
Sources: Expert Review
Differences of Sex Development v0.42 TSPYL1 Crystle Lee reviewed gene: TSPYL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 15273283, 19463995, 22137496, 25449952, 16418600; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome (MIM#608800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.42 WNT4 Zornitza Stark Marked gene: WNT4 as ready
Differences of Sex Development v0.42 WNT4 Zornitza Stark Gene: wnt4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.42 WNT4 Zornitza Stark Phenotypes for gene: WNT4 were changed from to Mullerian aplasia and hyperandrogenism (MIM#158330)
Differences of Sex Development v0.41 WNT4 Zornitza Stark Publications for gene: WNT4 were set to
Differences of Sex Development v0.40 WNT4 Zornitza Stark Mode of inheritance for gene: WNT4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.39 WNT4 Zornitza Stark Classified gene: WNT4 as Amber List (moderate evidence)
Differences of Sex Development v0.39 WNT4 Zornitza Stark Gene: wnt4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.38 ZFPM2 Zornitza Stark reviewed gene: ZFPM2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Differences of Sex Development v0.38 ZFPM2 Zornitza Stark Marked gene: ZFPM2 as ready
Differences of Sex Development v0.38 ZFPM2 Zornitza Stark Gene: zfpm2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.38 ZFPM2 Zornitza Stark Phenotypes for gene: ZFPM2 were changed from to 46XY sex reversal 9 (MIM#616067)
Differences of Sex Development v0.37 ZFPM2 Zornitza Stark Publications for gene: ZFPM2 were set to
Differences of Sex Development v0.36 ZFPM2 Zornitza Stark Mode of inheritance for gene: ZFPM2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.35 ZFPM2 Zornitza Stark Classified gene: ZFPM2 as Red List (low evidence)
Differences of Sex Development v0.35 ZFPM2 Zornitza Stark Gene: zfpm2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.34 ZFPM2 Zornitza Stark Tag refuted tag was added to gene: ZFPM2.
Differences of Sex Development v0.34 WNT4 Crystle Lee reviewed gene: WNT4: Rating: AMBER; Mode of pathogenicity: None; Publications: 22503279, 21377155, 16959810; Phenotypes: Mullerian aplasia and hyperandrogenism (MIM#158330); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Differences of Sex Development v0.34 ZFPM2 Crystle Lee reviewed gene: ZFPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24549039, 27899157, 31962012, 12223418; Phenotypes: 46XY sex reversal 9 (MIM#616067); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Differences of Sex Development v0.34 WDR11 Teresa Zhao reviewed gene: WDR11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20887964, PMID: 29263200; Phenotypes: Hypogonadotropic hypogonadism 14 with or without anosmia, MIM#614858; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Marked gene: FLRT3 as ready
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Added comment: Comment when marking as ready: Oligogenic inheritance postulated. I also note one of the variants, Gln69Lys is present in 7 individuals in gnomad.
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Marked gene: FLRT3 as ready
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.34 FLRT3 Zornitza Stark Phenotypes for gene: FLRT3 were changed from to Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271)
Differences of Sex Development v0.33 FLRT3 Zornitza Stark Publications for gene: FLRT3 were set to
Differences of Sex Development v0.32 FLRT3 Zornitza Stark Classified gene: FLRT3 as Red List (low evidence)
Differences of Sex Development v0.32 FLRT3 Zornitza Stark Gene: flrt3 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.31 FLRT3 Lauren Akesson reviewed gene: FLRT3: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 23643382, 31200363; Phenotypes: Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271); Mode of inheritance: Unknown
Differences of Sex Development v0.31 ESR2 Bryony Thompson gene: ESR2 was added
gene: ESR2 was added to Disorders of Sex Differentiation. Sources: Literature
Mode of inheritance for gene: ESR2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ESR2 were set to 29261182; 9861029
Phenotypes for gene: ESR2 were set to 46,XY Disorders of Sex Development
Review for gene: ESR2 was set to AMBER
Added comment: A homozygous indel (Asn181del) was identified in a syndromic case with 46,XY DSD, and 2 heterozygous missense variants were identified in 2 non-syndromic cases with 46,XY DSD. Asn181del and Leu426Arg were found to have significantly increased transcriptional activation in in vitro luciferase assays. Esrb null male mice showed no overt abnormalities and reproduced normally. Older mutant males displayed signs of prostate and bladder hyperplasia.
Sources: Literature
Differences of Sex Development v0.30 NR2F2 Zornitza Stark Marked gene: NR2F2 as ready
Differences of Sex Development v0.30 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.30 NR2F2 Zornitza Stark Classified gene: NR2F2 as Green List (high evidence)
Differences of Sex Development v0.30 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.29 NR2F2 Zornitza Stark gene: NR2F2 was added
gene: NR2F2 was added to Disorders of Sex Differentiation. Sources: Expert list
Mode of inheritance for gene: NR2F2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NR2F2 were set to 29478779; 31687637
Phenotypes for gene: NR2F2 were set to 46,XX disorder of sex development (DSD) and congenital heart defects
Review for gene: NR2F2 was set to GREEN
Added comment: Four unrelated individuals reported. Note two had the same 7bp deletion, c.97_103delCCGCCCG, NM_021005.3, and the third individual had an adjacent deletion, c.103_109delGGCGCCC, NM_021005.3. All three were of very different ancestries, making founder effect unlikely. Fourth individual had a larger deletion encompassing this gene. Gene is also linked with isolated CHD (Congenital heart defects, multiple types, 4, MIM# 615779)
Sources: Expert list
Differences of Sex Development v0.28 KLB Zornitza Stark Marked gene: KLB as ready
Differences of Sex Development v0.28 KLB Zornitza Stark Gene: klb has been classified as Green List (High Evidence).
Differences of Sex Development v0.28 KLB Zornitza Stark Classified gene: KLB as Green List (high evidence)
Differences of Sex Development v0.28 KLB Zornitza Stark Gene: klb has been classified as Green List (High Evidence).
Differences of Sex Development v0.27 KLB Zornitza Stark gene: KLB was added
gene: KLB was added to Disorders of Sex Differentiation. Sources: Literature
Mode of inheritance for gene: KLB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLB were set to 28754744
Phenotypes for gene: KLB were set to Hypogonadotropic hypogonadism
Review for gene: KLB was set to GREEN
Added comment: Seven heterozygous loss‐of‐function KLB mutations in 13 individuals reported. In mice, lack of Klb led to delayed puberty, altered estrous cyclicity, and subfertility due to a hypothalamic defect associated with inability of GnRH neurons to release GnRH in response to FGF21. Functional analysis showed decreased activity in response to FGF21 and FGF8. KLB is an obligate coreceptor for FGF21 alongside FGFR1.
Sources: Literature
Differences of Sex Development v0.26 NDNF Zornitza Stark Marked gene: NDNF as ready
Differences of Sex Development v0.26 NDNF Zornitza Stark Gene: ndnf has been classified as Green List (High Evidence).
Differences of Sex Development v0.26 NDNF Zornitza Stark Classified gene: NDNF as Green List (high evidence)
Differences of Sex Development v0.26 NDNF Zornitza Stark Gene: ndnf has been classified as Green List (High Evidence).
Differences of Sex Development v0.25 NDNF Zornitza Stark gene: NDNF was added
gene: NDNF was added to Disorders of Sex Differentiation. Sources: Literature
Mode of inheritance for gene: NDNF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NDNF were set to 31883645
Phenotypes for gene: NDNF were set to Congenital hypogonadotropic hypogonadism (CHH)
Review for gene: NDNF was set to GREEN
Added comment: Three heterozygous protein-truncating variants and one heterozygous missense variant identified in a cohort of 240 unrelated IHH patients. The authors also provided supporting evidence from animal models.
Sources: Literature
Differences of Sex Development v0.24 MYRF Zornitza Stark Marked gene: MYRF as ready
Differences of Sex Development v0.24 MYRF Zornitza Stark Gene: myrf has been classified as Green List (High Evidence).
Differences of Sex Development v0.24 MYRF Zornitza Stark Classified gene: MYRF as Green List (high evidence)
Differences of Sex Development v0.24 MYRF Zornitza Stark Gene: myrf has been classified as Green List (High Evidence).
Differences of Sex Development v0.23 DHX37 Zornitza Stark Marked gene: DHX37 as ready
Differences of Sex Development v0.23 DHX37 Zornitza Stark Gene: dhx37 has been classified as Green List (High Evidence).
Differences of Sex Development v0.23 DHX37 Zornitza Stark Classified gene: DHX37 as Green List (high evidence)
Differences of Sex Development v0.23 DHX37 Zornitza Stark Gene: dhx37 has been classified as Green List (High Evidence).
Differences of Sex Development v0.22 DHX37 Zornitza Stark gene: DHX37 was added
gene: DHX37 was added to Disorders of Sex Differentiation. Sources: Literature
Mode of inheritance for gene: DHX37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX37 were set to 31337883; 31745530
Phenotypes for gene: DHX37 were set to 46,XY gonadal dysgenesis; testicular regression syndrome (TRS)
Review for gene: DHX37 was set to GREEN
Added comment: Seventeen individuals reported in two studies.
Sources: Literature
Differences of Sex Development v0.21 MYRF Ain Roesley gene: MYRF was added
gene: MYRF was added to Disorders of Sex Differentiation. Sources: Literature
Mode of inheritance for gene: MYRF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYRF were set to PMID: 30985895
Phenotypes for gene: MYRF were set to disorders of sex development
Review for gene: MYRF was set to GREEN
Added comment: PMID: 30985895; 4 unrelated families with de novo variants. 1 family includes monozygotic twins
Sources: Literature
Differences of Sex Development v0.21 RXFP2 Zornitza Stark Marked gene: RXFP2 as ready
Differences of Sex Development v0.21 RXFP2 Zornitza Stark Gene: rxfp2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.21 RXFP2 Zornitza Stark Phenotypes for gene: RXFP2 were changed from to Cryptorchidism
Differences of Sex Development v0.20 RXFP2 Zornitza Stark Publications for gene: RXFP2 were set to
Differences of Sex Development v0.19 RXFP2 Zornitza Stark Mode of inheritance for gene: RXFP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.18 RXFP2 Zornitza Stark Classified gene: RXFP2 as Red List (low evidence)
Differences of Sex Development v0.18 RXFP2 Zornitza Stark Gene: rxfp2 has been classified as Red List (Low Evidence).
Differences of Sex Development v0.17 RXFP2 Zornitza Stark reviewed gene: RXFP2: Rating: RED; Mode of pathogenicity: None; Publications: 31167797, 20963592; Phenotypes: Cryptorchidism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.17 DHH Zornitza Stark Marked gene: DHH as ready
Differences of Sex Development v0.17 DHH Zornitza Stark Gene: dhh has been classified as Green List (High Evidence).
Differences of Sex Development v0.17 DHH Zornitza Stark Phenotypes for gene: DHH were changed from to 46XY partial gonadal dysgenesis, with minifascicular neuropathy, MIM# 607080
Differences of Sex Development v0.16 DHH Zornitza Stark Publications for gene: DHH were set to
Differences of Sex Development v0.15 DHH Zornitza Stark Mode of inheritance for gene: DHH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.14 DHH Naomi Baker reviewed gene: DHH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31018998, 29471294, 11017805.; Phenotypes: gonadal dysgenesis, minifascicular neuropathy.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.14 PROKR2 Zornitza Stark reviewed gene: PROKR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18826963, 29161432; Phenotypes: Hypogonadotropic hypogonadism 3 with or without anosmia, MIM# 244200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences of Sex Development v0.14 GNRHR Zornitza Stark Marked gene: GNRHR as ready
Differences of Sex Development v0.14 GNRHR Zornitza Stark Gene: gnrhr has been classified as Green List (High Evidence).
Differences of Sex Development v0.14 GNRHR Zornitza Stark Phenotypes for gene: GNRHR were changed from to Hypogonadotropic hypogonadism 7 without anosmia, MIM#146110
Differences of Sex Development v0.13 GNRHR Zornitza Stark Publications for gene: GNRHR were set to
Differences of Sex Development v0.12 GNRHR Zornitza Stark Mode of inheritance for gene: GNRHR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.11 GNRHR Zornitza Stark reviewed gene: GNRHR: Rating: GREEN; Mode of pathogenicity: None; Publications: 28348023, 9371856; Phenotypes: Hypogonadotropic hypogonadism 7 without anosmia, MIM#146110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.11 CYP21A2 Zornitza Stark Marked gene: CYP21A2 as ready
Differences of Sex Development v0.11 CYP21A2 Zornitza Stark Gene: cyp21a2 has been classified as Green List (High Evidence).
Differences of Sex Development v0.11 CYP21A2 Zornitza Stark Phenotypes for gene: CYP21A2 were changed from to Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency, 201910; Hyperandrogenism, nonclassic type, due to 21-hydroxylase deficiency, 201910
Differences of Sex Development v0.10 CYP21A2 Zornitza Stark Mode of inheritance for gene: CYP21A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.9 CYP21A2 Zornitza Stark reviewed gene: CYP21A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency, 201910, Hyperandrogenism, nonclassic type, due to 21-hydroxylase deficiency, 201910; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.9 SOX3 Zornitza Stark Marked gene: SOX3 as ready
Differences of Sex Development v0.9 SOX3 Zornitza Stark Gene: sox3 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.9 SOX3 Zornitza Stark Classified gene: SOX3 as Amber List (moderate evidence)
Differences of Sex Development v0.9 SOX3 Zornitza Stark Gene: sox3 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.8 SOX3 Zornitza Stark gene: SOX3 was added
gene: SOX3 was added to Disorders of Sex Differentiation. Sources: Expert Review
SV/CNV tags were added to gene: SOX3.
Mode of inheritance for gene: SOX3 was set to Other
Publications for gene: SOX3 were set to 21183788; 22678921; 25781358; 31523625
Phenotypes for gene: SOX3 were set to XX male sex reversal
Mode of pathogenicity for gene: SOX3 was set to Other
Review for gene: SOX3 was set to AMBER
Added comment: Multiple individuals reported; animal model: association is with structural variants, primarily duplications.
Sources: Expert Review
Differences of Sex Development v0.7 PPP1R12A Zornitza Stark Publications for gene: PPP1R12A were set to
Differences of Sex Development v0.6 PPP1R12A Zornitza Stark edited their review of gene: PPP1R12A: Changed rating: GREEN; Changed publications: 31883643
Differences of Sex Development v0.6 Zornitza Stark Panel name changed from Disorders of Sex Differentiation_VCGS to Disorders of Sex Differentiation
Panel types changed to Victorian Clinical Genetics Services
Differences of Sex Development v0.5 PPP1R12A Zornitza Stark Marked gene: PPP1R12A as ready
Differences of Sex Development v0.5 PPP1R12A Zornitza Stark Added comment: Comment when marking as ready: Now published; 12 individuals, upgraded to Green.
Differences of Sex Development v0.5 PPP1R12A Zornitza Stark Gene: ppp1r12a has been classified as Green List (High Evidence).
Differences of Sex Development v0.5 PPP1R12A Zornitza Stark Classified gene: PPP1R12A as Green List (high evidence)
Differences of Sex Development v0.5 PPP1R12A Zornitza Stark Gene: ppp1r12a has been classified as Green List (High Evidence).
Differences of Sex Development v0.4 PBX1 Zornitza Stark Marked gene: PBX1 as ready
Differences of Sex Development v0.4 PBX1 Zornitza Stark Gene: pbx1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.4 PBX1 Zornitza Stark Classified gene: PBX1 as Amber List (moderate evidence)
Differences of Sex Development v0.4 PBX1 Zornitza Stark Gene: pbx1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.3 PBX1 Zornitza Stark gene: PBX1 was added
gene: PBX1 was added to Disorders of Sex Differentiation_VCGS. Sources: Literature
Mode of inheritance for gene: PBX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PBX1 were set to 31302614; 31058389
Phenotypes for gene: PBX1 were set to 46, XY gonadal dysgenesis
Review for gene: PBX1 was set to AMBER
Added comment: Two individuals reported with mono allelic variants in this gene and 46,XY gonadal dysgenesis.
Sources: Literature
Differences of Sex Development v0.2 PPP1R12A Zornitza Stark Marked gene: PPP1R12A as ready
Differences of Sex Development v0.2 PPP1R12A Zornitza Stark Gene: ppp1r12a has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.2 PPP1R12A Zornitza Stark Phenotypes for gene: PPP1R12A were changed from to Intellectual disability; holoprosencephaly; disorder of sex development
Differences of Sex Development v0.1 PPP1R12A Zornitza Stark Mode of inheritance for gene: PPP1R12A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.1 PPP1R12A Zornitza Stark Classified gene: PPP1R12A as Amber List (moderate evidence)
Differences of Sex Development v0.1 PPP1R12A Zornitza Stark Gene: ppp1r12a has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.0 PPP1R12A Zornitza Stark reviewed gene: PPP1R12A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual disability, holoprosencephaly, disorder of sex development; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Differences of Sex Development v0.0 ZFPM2 Zornitza Stark gene: ZFPM2 was added
gene: ZFPM2 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ZFPM2 was set to Unknown
Differences of Sex Development v0.0 WT1 Zornitza Stark gene: WT1 was added
gene: WT1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: WT1 was set to Unknown
Differences of Sex Development v0.0 WNT4 Zornitza Stark gene: WNT4 was added
gene: WNT4 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: WNT4 was set to Unknown
Differences of Sex Development v0.0 WDR11 Zornitza Stark gene: WDR11 was added
gene: WDR11 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: WDR11 was set to Unknown
Differences of Sex Development v0.0 TSPYL1 Zornitza Stark gene: TSPYL1 was added
gene: TSPYL1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TSPYL1 was set to Unknown
Differences of Sex Development v0.0 TAC3 Zornitza Stark gene: TAC3 was added
gene: TAC3 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TAC3 was set to Unknown
Differences of Sex Development v0.0 STAR Zornitza Stark gene: STAR was added
gene: STAR was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: STAR was set to Unknown
Differences of Sex Development v0.0 SRY Zornitza Stark gene: SRY was added
gene: SRY was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SRY was set to Unknown
Differences of Sex Development v0.0 SRD5A2 Zornitza Stark gene: SRD5A2 was added
gene: SRD5A2 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SRD5A2 was set to Unknown
Differences of Sex Development v0.0 SOX9 Zornitza Stark gene: SOX9 was added
gene: SOX9 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SOX9 was set to Unknown
Differences of Sex Development v0.0 RXFP2 Zornitza Stark gene: RXFP2 was added
gene: RXFP2 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RXFP2 was set to Unknown
Differences of Sex Development v0.0 RSPO1 Zornitza Stark gene: RSPO1 was added
gene: RSPO1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RSPO1 was set to Unknown
Differences of Sex Development v0.0 PROP1 Zornitza Stark gene: PROP1 was added
gene: PROP1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PROP1 was set to Unknown
Differences of Sex Development v0.0 PROKR2 Zornitza Stark gene: PROKR2 was added
gene: PROKR2 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PROKR2 was set to Unknown
Differences of Sex Development v0.0 PROK2 Zornitza Stark gene: PROK2 was added
gene: PROK2 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PROK2 was set to Unknown
Differences of Sex Development v0.0 PPP1R12A Zornitza Stark gene: PPP1R12A was added
gene: PPP1R12A was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PPP1R12A was set to Unknown
Differences of Sex Development v0.0 POR Zornitza Stark gene: POR was added
gene: POR was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: POR was set to Unknown
Differences of Sex Development v0.0 PCSK1 Zornitza Stark gene: PCSK1 was added
gene: PCSK1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PCSK1 was set to Unknown
Differences of Sex Development v0.0 NR5A1 Zornitza Stark gene: NR5A1 was added
gene: NR5A1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NR5A1 was set to Unknown
Differences of Sex Development v0.0 NR3C1 Zornitza Stark gene: NR3C1 was added
gene: NR3C1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NR3C1 was set to Unknown
Differences of Sex Development v0.0 NR0B1 Zornitza Stark gene: NR0B1 was added
gene: NR0B1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NR0B1 was set to Unknown
Differences of Sex Development v0.0 MKKS Zornitza Stark gene: MKKS was added
gene: MKKS was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MKKS was set to Unknown
Differences of Sex Development v0.0 MAP3K1 Zornitza Stark gene: MAP3K1 was added
gene: MAP3K1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MAP3K1 was set to Unknown
Differences of Sex Development v0.0 MAMLD1 Zornitza Stark gene: MAMLD1 was added
gene: MAMLD1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MAMLD1 was set to Unknown
Differences of Sex Development v0.0 LHX3 Zornitza Stark gene: LHX3 was added
gene: LHX3 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LHX3 was set to Unknown
Differences of Sex Development v0.0 LHCGR Zornitza Stark gene: LHCGR was added
gene: LHCGR was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LHCGR was set to Unknown
Differences of Sex Development v0.0 LHB Zornitza Stark gene: LHB was added
gene: LHB was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LHB was set to Unknown
Differences of Sex Development v0.0 LEPR Zornitza Stark gene: LEPR was added
gene: LEPR was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LEPR was set to Unknown
Differences of Sex Development v0.0 LEP Zornitza Stark gene: LEP was added
gene: LEP was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LEP was set to Unknown
Differences of Sex Development v0.0 KISS1R Zornitza Stark gene: KISS1R was added
gene: KISS1R was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: KISS1R was set to Unknown
Differences of Sex Development v0.0 INSL3 Zornitza Stark gene: INSL3 was added
gene: INSL3 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: INSL3 was set to Unknown
Differences of Sex Development v0.0 IL17RD Zornitza Stark gene: IL17RD was added
gene: IL17RD was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: IL17RD was set to Unknown
Differences of Sex Development v0.0 HSD3B2 Zornitza Stark gene: HSD3B2 was added
gene: HSD3B2 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: HSD3B2 was set to Unknown
Differences of Sex Development v0.0 HSD17B4 Zornitza Stark gene: HSD17B4 was added
gene: HSD17B4 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: HSD17B4 was set to Unknown
Differences of Sex Development v0.0 HSD17B3 Zornitza Stark gene: HSD17B3 was added
gene: HSD17B3 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: HSD17B3 was set to Unknown
Differences of Sex Development v0.0 HS6ST1 Zornitza Stark gene: HS6ST1 was added
gene: HS6ST1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: HS6ST1 was set to Unknown
Differences of Sex Development v0.0 HOXA13 Zornitza Stark gene: HOXA13 was added
gene: HOXA13 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: HOXA13 was set to Unknown
Differences of Sex Development v0.0 HESX1 Zornitza Stark gene: HESX1 was added
gene: HESX1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: HESX1 was set to Unknown
Differences of Sex Development v0.0 GNRHR Zornitza Stark gene: GNRHR was added
gene: GNRHR was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GNRHR was set to Unknown
Differences of Sex Development v0.0 GNRH1 Zornitza Stark gene: GNRH1 was added
gene: GNRH1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GNRH1 was set to Unknown
Differences of Sex Development v0.0 GATA4 Zornitza Stark gene: GATA4 was added
gene: GATA4 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GATA4 was set to Unknown
Differences of Sex Development v0.0 FSHR Zornitza Stark gene: FSHR was added
gene: FSHR was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FSHR was set to Unknown
Differences of Sex Development v0.0 FSHB Zornitza Stark gene: FSHB was added
gene: FSHB was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FSHB was set to Unknown
Differences of Sex Development v0.0 FLRT3 Zornitza Stark gene: FLRT3 was added
gene: FLRT3 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FLRT3 was set to Unknown
Differences of Sex Development v0.0 FGFR2 Zornitza Stark gene: FGFR2 was added
gene: FGFR2 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FGFR2 was set to Unknown
Differences of Sex Development v0.0 FGFR1 Zornitza Stark gene: FGFR1 was added
gene: FGFR1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FGFR1 was set to Unknown
Differences of Sex Development v0.0 FGF8 Zornitza Stark gene: FGF8 was added
gene: FGF8 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FGF8 was set to Unknown
Differences of Sex Development v0.0 FGF17 Zornitza Stark gene: FGF17 was added
gene: FGF17 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FGF17 was set to Unknown
Differences of Sex Development v0.0 FEZF1 Zornitza Stark gene: FEZF1 was added
gene: FEZF1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FEZF1 was set to Unknown
Differences of Sex Development v0.0 DUSP6 Zornitza Stark gene: DUSP6 was added
gene: DUSP6 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DUSP6 was set to Unknown
Differences of Sex Development v0.0 DHH Zornitza Stark gene: DHH was added
gene: DHH was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DHH was set to Unknown
Differences of Sex Development v0.0 DHCR7 Zornitza Stark gene: DHCR7 was added
gene: DHCR7 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DHCR7 was set to Unknown
Differences of Sex Development v0.0 DHCR24 Zornitza Stark gene: DHCR24 was added
gene: DHCR24 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DHCR24 was set to Unknown
Differences of Sex Development v0.0 CYP21A2 Zornitza Stark gene: CYP21A2 was added
gene: CYP21A2 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CYP21A2 was set to Unknown
Differences of Sex Development v0.0 CYP19A1 Zornitza Stark gene: CYP19A1 was added
gene: CYP19A1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CYP19A1 was set to Unknown
Differences of Sex Development v0.0 CYP17A1 Zornitza Stark gene: CYP17A1 was added
gene: CYP17A1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CYP17A1 was set to Unknown
Differences of Sex Development v0.0 CYP11B1 Zornitza Stark gene: CYP11B1 was added
gene: CYP11B1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CYP11B1 was set to Unknown
Differences of Sex Development v0.0 CYP11A1 Zornitza Stark gene: CYP11A1 was added
gene: CYP11A1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CYP11A1 was set to Unknown
Differences of Sex Development v0.0 CHD7 Zornitza Stark gene: CHD7 was added
gene: CHD7 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CHD7 was set to Unknown
Differences of Sex Development v0.0 CDKN1C Zornitza Stark gene: CDKN1C was added
gene: CDKN1C was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CDKN1C was set to Unknown
Differences of Sex Development v0.0 CBX2 Zornitza Stark gene: CBX2 was added
gene: CBX2 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CBX2 was set to Unknown
Differences of Sex Development v0.0 BMP15 Zornitza Stark gene: BMP15 was added
gene: BMP15 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: BMP15 was set to Unknown
Differences of Sex Development v0.0 ATRX Zornitza Stark gene: ATRX was added
gene: ATRX was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ATRX was set to Unknown
Differences of Sex Development v0.0 ATF3 Zornitza Stark gene: ATF3 was added
gene: ATF3 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ATF3 was set to Unknown
Differences of Sex Development v0.0 ARX Zornitza Stark gene: ARX was added
gene: ARX was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ARX was set to Unknown
Differences of Sex Development v0.0 AR Zornitza Stark gene: AR was added
gene: AR was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AR was set to Unknown
Differences of Sex Development v0.0 ANOS1 Zornitza Stark gene: ANOS1 was added
gene: ANOS1 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ANOS1 was set to Unknown
Differences of Sex Development v0.0 AMHR2 Zornitza Stark gene: AMHR2 was added
gene: AMHR2 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AMHR2 was set to Unknown
Differences of Sex Development v0.0 AMH Zornitza Stark gene: AMH was added
gene: AMH was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AMH was set to Unknown
Differences of Sex Development v0.0 AKR1C4 Zornitza Stark gene: AKR1C4 was added
gene: AKR1C4 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AKR1C4 was set to Unknown
Differences of Sex Development v0.0 AKR1C2 Zornitza Stark gene: AKR1C2 was added
gene: AKR1C2 was added to Disorders of Sex Differentiation_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AKR1C2 was set to Unknown
Differences of Sex Development v0.0 Zornitza Stark Added panel Disorders of Sex Differentiation_VCGS