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| Imprinting disorders v1.3 | GNAS-AS1 | Zornitza Stark Marked gene: GNAS-AS1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v1.3 | GNAS-AS1 | Zornitza Stark Gene: gnas-as1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v1.3 | GNAS-AS1 | Zornitza Stark Tag SV/CNV tag was added to gene: GNAS-AS1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v1.3 | GNAS-AS1 | Zornitza Stark Classified gene: GNAS-AS1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v1.3 | GNAS-AS1 | Zornitza Stark Gene: gnas-as1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v1.2 | GNAS-AS1 |
Anna Le Fevre changed review comment from: Single report of a AD-PHP-Ib kindred with a maternally inherited deletion limited to GNAS-AS1 (Chillambhi et al 2010). Further reports of maternally inherited deletions including regions of both GNAS-AS1 and exon NESP55. Note, this non-coding RNA is paternally expressed, but causative deletions have been maternally inherited. Reports of two AD-PHP-Ib kindreds with 4-kb microdeletions comprising the entire NESP55 DMR. These include exon NESP55 (GNAS encoded) and exons 3 and 4 of the GNAS antisense transcript. It remains unknown whether the observed imprinting changes and PTH resistance in these patients result from the loss of NESP55 expression or the loss of the deleted genomic region. Chillambhi et al reported a AD-PHP-Ib kindred and identified a novel deletion that exclusively affects exons encoding the GNAS-AS. Overlapping with the previously identified deletions by approximately 1.5 kb. Unlike the previously identified deletions associated with AD-PHP-Ib, the novel deletion not only disrupts methylation of three GNAS DMRs (A/B, AS, and XL) after maternal transmission but also appears to partially alter methylation of the NESP55 and the A/B DMRs after paternal transmission, revealing a novel cis-acting mechanism that governs imprinting on both parental alleles. Rezwan et al reported two further families with 33bp and 40bp deletions intronic to both NESP55 and NESP-AS. These were not definitively causative of the phenotype in the family. Sources: Literature; to: Single report of a AD-PHP-Ib kindred with a maternally inherited deletion limited to GNAS-AS1 (Chillambhi et al 2010). Further reports of maternally inherited deletions including regions of both GNAS-AS1 and exon NESP55. Although deletions in this region appear to be causative of AD-PHP-Ib, evidence for deletions limited to only GNAS-AS1 is limited to date. Note, this non-coding RNA is paternally expressed, but causative deletions have been maternally inherited. Reports of two AD-PHP-Ib kindreds with 4-kb microdeletions comprising the entire NESP55 DMR. These include exon NESP55 (GNAS encoded) and exons 3 and 4 of the GNAS antisense transcript. It remains unknown whether the observed imprinting changes and PTH resistance in these patients result from the loss of NESP55 expression or the loss of the deleted genomic region. Chillambhi et al reported a AD-PHP-Ib kindred and identified a novel deletion that exclusively affects exons encoding the GNAS-AS. Overlapping with the previously identified deletions by approximately 1.5 kb. Unlike the previously identified deletions associated with AD-PHP-Ib, the novel deletion not only disrupts methylation of three GNAS DMRs (A/B, AS, and XL) after maternal transmission but also appears to partially alter methylation of the NESP55 and the A/B DMRs after paternal transmission, revealing a novel cis-acting mechanism that governs imprinting on both parental alleles. Rezwan et al reported two further families with 33bp and 40bp deletions intronic to both NESP55 and NESP-AS. These were not definitively causative of the phenotype in the family. Sources: Literature |
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| Imprinting disorders v1.2 | GNAS-AS1 |
Anna Le Fevre gene: GNAS-AS1 was added gene: GNAS-AS1 was added to Imprinting disorders. Sources: Literature Mode of inheritance for gene: GNAS-AS1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) Publications for gene: GNAS-AS1 were set to PMID: 22378814; 15592469; 29959430; 25005734 Phenotypes for gene: GNAS-AS1 were set to Pseudohypoparathyroidism type 1b MIM no: 603233 Review for gene: GNAS-AS1 was set to RED Added comment: Single report of a AD-PHP-Ib kindred with a maternally inherited deletion limited to GNAS-AS1 (Chillambhi et al 2010). Further reports of maternally inherited deletions including regions of both GNAS-AS1 and exon NESP55. Note, this non-coding RNA is paternally expressed, but causative deletions have been maternally inherited. Reports of two AD-PHP-Ib kindreds with 4-kb microdeletions comprising the entire NESP55 DMR. These include exon NESP55 (GNAS encoded) and exons 3 and 4 of the GNAS antisense transcript. It remains unknown whether the observed imprinting changes and PTH resistance in these patients result from the loss of NESP55 expression or the loss of the deleted genomic region. Chillambhi et al reported a AD-PHP-Ib kindred and identified a novel deletion that exclusively affects exons encoding the GNAS-AS. Overlapping with the previously identified deletions by approximately 1.5 kb. Unlike the previously identified deletions associated with AD-PHP-Ib, the novel deletion not only disrupts methylation of three GNAS DMRs (A/B, AS, and XL) after maternal transmission but also appears to partially alter methylation of the NESP55 and the A/B DMRs after paternal transmission, revealing a novel cis-acting mechanism that governs imprinting on both parental alleles. Rezwan et al reported two further families with 33bp and 40bp deletions intronic to both NESP55 and NESP-AS. These were not definitively causative of the phenotype in the family. Sources: Literature |
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| Imprinting disorders v1.1 | STX16 | Zornitza Stark Marked gene: STX16 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v1.1 | STX16 | Zornitza Stark Gene: stx16 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v1.1 | STX16 | Zornitza Stark Classified gene: STX16 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v1.1 | STX16 | Zornitza Stark Gene: stx16 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v1.0 | STX16 | Zornitza Stark Tag SV/CNV tag was added to gene: STX16. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v1.0 | STX16 |
Anna Le Fevre gene: STX16 was added gene: STX16 was added to Imprinting disorders. Sources: Literature Mode of inheritance for gene: STX16 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) Publications for gene: STX16 were set to PMID: 1456170; 15579741; 15800843; 33320452; 32337648; 33247854; 29959430 Phenotypes for gene: STX16 were set to Pseudohypoparathyroidism type 1b MIM no: 603233 Review for gene: STX16 was set to GREEN Added comment: Multiple reports of a PHP-Ib phenotype. Caused in most cases by a maternally inherited 3-kb, 4.4-kb or larger deletion involving STX16, which is associated with loss of methylation (LOM) at GNAS exon A/B DMR (also referred to as exon 1A or GNAS A/B:TSS-DMR). Of PHP1B cases, 15–20% are familial, with an autosomal dominant mode of inheritance (AD-PHP1B) through the maternal lineage. In this familial form, the methylation defect is usually limited to loss of methylation at GNAS A/B:TSS-DMR, secondary to a 3 kb microdeletion on the maternal allele of cis-acting control elements within STX16. Other maternally inherited deletions and duplications have also been identified in some rare familial cases affecting either an isolated GNAS A/B:TSS-DMR or all four DMRs (Nature review, PMID 29959430) STX16 is not clearly an imprinted gene, but only maternally inherited deletions are associated with this phenotype. Deletions in this gene are thought to disrupt cis-acting regulation of GNAS expression. Sources: Literature |
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| Imprinting disorders v1.0 | Zornitza Stark promoted panel to version 1.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.40 | SGCE | Zornitza Stark Phenotypes for gene: SGCE were changed from Affected tissue: brain; Phenotype resulting from under expression: upper body myoclonus, dystonia to Affected tissue: brain; Phenotype resulting from under expression: upper body myoclonus, dystonia; Dystonia-11, myoclonic, MIM# 159900 MONDO:0008044 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.39 | SGCE | Zornitza Stark Marked gene: SGCE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.39 | SGCE | Zornitza Stark Gene: sgce has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.39 | SGCE | Zornitza Stark Publications for gene: SGCE were set to 25209853; 23237735; 23365103; 30794780; 11528394; 12325078; 17200151 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.38 | SGCE | Zornitza Stark Publications for gene: SGCE were set to PMID: 25209853; 23237735; 23365103; http://igc.otago.ac.nz/home.html; 30794780 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.36 | ZAR1 | Zornitza Stark Marked gene: ZAR1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.36 | ZAR1 | Zornitza Stark Gene: zar1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.36 | ZAR1 | Zornitza Stark Classified gene: ZAR1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.36 | ZAR1 | Zornitza Stark Gene: zar1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.35 | ZAR1 | Zornitza Stark reviewed gene: ZAR1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.35 | UHRF1 | Zornitza Stark Classified gene: UHRF1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.35 | UHRF1 | Zornitza Stark Gene: uhrf1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.34 | UHRF1 | Zornitza Stark reviewed gene: UHRF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.34 | UHRF1 | Zornitza Stark Marked gene: UHRF1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.34 | UHRF1 | Zornitza Stark Gene: uhrf1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.34 | UHRF1 | Zornitza Stark Classified gene: UHRF1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.34 | UHRF1 | Zornitza Stark Gene: uhrf1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.33 | MAGEL2 | Zornitza Stark Marked gene: MAGEL2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.33 | MAGEL2 | Zornitza Stark Gene: magel2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.33 | MAGEL2 | Zornitza Stark Phenotypes for gene: MAGEL2 were changed from Schaaf-Yang syndrome; Chitayat-Hall Syndrome to Schaaf-Yang syndrome, MIM# 615547; Chitayat-Hall Syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.32 | MAGEL2 | Zornitza Stark Classified gene: MAGEL2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.32 | MAGEL2 | Zornitza Stark Gene: magel2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.31 | MAGEL2 | Zornitza Stark reviewed gene: MAGEL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Schaaf-Yang syndrome, MIM# 615547; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.31 | KCNQ1 | Zornitza Stark Marked gene: KCNQ1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.31 | KCNQ1 | Zornitza Stark Gene: kcnq1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.31 | KCNQ1 | Zornitza Stark Publications for gene: KCNQ1 were set to PMID 30635621; 32393365; 30778172 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.30 | KCNQ1 | Zornitza Stark Classified gene: KCNQ1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.30 | KCNQ1 | Zornitza Stark Gene: kcnq1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.29 | L3MBTL1 | Zornitza Stark Marked gene: L3MBTL1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.29 | L3MBTL1 | Zornitza Stark Gene: l3mbtl1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.29 | L3MBTL1 | Zornitza Stark Publications for gene: L3MBTL1 were set to http://igc.otago.ac.nz/home.html; 23543057; PMID: 15123827; 30794780 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.28 | L3MBTL1 | Zornitza Stark Classified gene: L3MBTL1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.28 | L3MBTL1 | Zornitza Stark Gene: l3mbtl1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.27 | KCNQ1OT1 | Zornitza Stark Publications for gene: KCNQ1OT1 were set to 22205991; 15372379; 23511928; 30794780; 29377879; 10220444; 32447323; 33177595; 29047350 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.26 | KCNQ1OT1 | Zornitza Stark Marked gene: KCNQ1OT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.26 | KCNQ1OT1 | Zornitza Stark Gene: kcnq1ot1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.26 | KCNQ1OT1 | Zornitza Stark Phenotypes for gene: KCNQ1OT1 were changed from Beckwith-Wiedemann syndrome OMIM:130650 to Beckwith-Wiedemann syndrome OMIM:130650; Russell-Silver Syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.25 | KCNQ1OT1 | Zornitza Stark Publications for gene: KCNQ1OT1 were set to 22205991; 15372379; 10220444; http://igc.otago.ac.nz/home.html; 23511928; 30794780 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.24 | KCNQ1OT1 | Zornitza Stark Classified gene: KCNQ1OT1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.24 | KCNQ1OT1 | Zornitza Stark Gene: kcnq1ot1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.23 | H19 | Zornitza Stark Marked gene: H19 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.23 | H19 | Zornitza Stark Gene: h19 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.23 | H19 | Zornitza Stark Classified gene: H19 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.23 | H19 | Zornitza Stark Gene: h19 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.22 | H19 | Zornitza Stark reviewed gene: H19: Rating: RED; Mode of pathogenicity: None; Publications: 20007505, 15743916, 23118352, 21863054, 21571108, 18245780, 24916376, 25943194; Phenotypes: Phenotypes resulting from gene over expression: Silver-Russell Syndrome (proven effects of dosage alteration rather than gene muation), Affected tissue: all, Phenotype resulting from under expression: Beckwith-Wiedemann Syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.22 | GNAS | Zornitza Stark Marked gene: GNAS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.22 | GNAS | Zornitza Stark Gene: gnas has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.22 | GNAS | Zornitza Stark Phenotypes for gene: GNAS were changed from Affected tissue: kidney, bone, brain; pseudopseudohypoparathyroidism; Phenotype resulting from under expression: Pseudohypoparathyroidism Type 1a to Affected tissue: kidney, bone, brain; pseudopseudohypoparathyroidism; Phenotype resulting from under expression: Pseudohypoparathyroidism Type 1a, MIM# 103580; Albright hereditary osteodystrophy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.21 | GNAS | Zornitza Stark Publications for gene: GNAS were set to 10980525; 11406605; 12024005; 15800843; 15181091; 9506752; 12024004; 15592469; 15592469; 11788646; 1944469; 2109828; 30794780 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.20 | GNAS | Zornitza Stark Publications for gene: GNAS were set to 10980525; [11406605; 12024005; 15800843]; 15181091; 9506752; 12024004; http://igc.otago.ac.nz/home.html; 15592469; [15592469; 11788646; 1944469; PMID: 2109828; 30794780 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.19 | GNAS | Zornitza Stark edited their review of gene: GNAS: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.19 | GNAS | Zornitza Stark reviewed gene: GNAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 15331575; Phenotypes: Pseudohypoparathyroidism Ia, MIM# 103580, Albright hereditary osteodystrophy, Pseudohypoparathyroidism Ib, MIM# 603233; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.19 | MAGEL2 |
Anna Le Fevre changed review comment from: MAGEL2 is a single-exon gene. Frameshift mutations may not cause nonsense-mediated decay, but instead a variety of truncated or elongated protein products. The pathogenicity of haploinsufficiency of the paternal allele is uncertain (ClinGen review 2018). A dominant-negative effect has been suggested. Haploinsufficiency may play a role. Sources: Literature; to: Multiple reports. MAGEL2 is a single-exon gene. Frameshift mutations may not cause nonsense-mediated decay, but instead a variety of truncated or elongated protein products. The pathogenicity of haploinsufficiency of the paternal allele is uncertain (ClinGen review 2018). A dominant-negative effect has been suggested. Haploinsufficiency may play a role. Sources: Literature |
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| Imprinting disorders v0.19 | OOEP | Zornitza Stark Marked gene: OOEP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.19 | OOEP | Zornitza Stark Gene: ooep has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.19 | OOEP | Zornitza Stark Classified gene: OOEP as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.19 | OOEP | Zornitza Stark Gene: ooep has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.18 | OOEP | Zornitza Stark reviewed gene: OOEP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.18 | ZNF445 | Zornitza Stark Marked gene: ZNF445 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.18 | ZNF445 | Zornitza Stark Gene: znf445 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.18 | ZNF445 | Zornitza Stark Classified gene: ZNF445 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.18 | ZNF445 | Zornitza Stark Gene: znf445 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.17 | ZNF445 | Zornitza Stark reviewed gene: ZNF445: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.17 | TLE6 | Zornitza Stark Marked gene: TLE6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.17 | TLE6 | Zornitza Stark Gene: tle6 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.17 | TLE6 | Zornitza Stark Classified gene: TLE6 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.17 | TLE6 | Zornitza Stark Gene: tle6 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.16 | NLRP7 | Zornitza Stark Publications for gene: NLRP7 were set to 19246479; 28916717; 31201414; 16462743; 29574422 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.15 | KHDC3L | Zornitza Stark Marked gene: KHDC3L as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.15 | KHDC3L | Zornitza Stark Gene: khdc3l has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.15 | KHDC3L | Zornitza Stark Phenotypes for gene: KHDC3L were changed from Hydatiform mold recurrent 2 MIM#614293 to Hydatiform mole recurrent 2 MIM#614293 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.14 | KHDC3L | Zornitza Stark Classified gene: KHDC3L as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.14 | KHDC3L | Zornitza Stark Gene: khdc3l has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.13 | KCNQ1 |
Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence. The KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5 is located within KCNQ1 intron 10. IC2 corresponds to the promoter of the long noncoding RNA KCNQ1OT1 and is methylated and inactive on the maternal chromosome. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the Beckwith-Wiedemann Syndrome (BWS) patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Pathogenic variants in KCNQ1 are associated with long-QT syndrome (LQTS) and can be inherited on the paternal or maternal allele. Loss of methylation (LOM) of IC2 has been reported in a small number of individuals with KCNQ1 germline variants which additionally cause LQTS. Valente et al (PMID 30635621) reported three individuals with LQTS, features of BWS and LOM at IC2 and maternally inherited KCNQ1 variants, two of which were demonstrated to affect KCNQ1 transcription upstream of IC2. Essinger et al (PMID 32393365) analysed KCNQ1 in 52 individuals with LOM at IC2 and identified one individual with a splice site variant causing premature transcription termination. Microdeletions of IC2 variably involving KCNQ1, CDKN1C and KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. LoF in CDKN1C is a known cause of BWS. Beygo et al (PMID 30778172) demonstrated that disruption of KCNQ1 prevents methylation of IC2 supporting the hypothesis that transcription of KCNQ1 is required for establishing the maternal methylation imprint at IC2. Sources: Literature; to: Proposed classification: Amber, pending further evidence. The KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5 is located within KCNQ1 intron 10. IC2 corresponds to the promoter of the long noncoding RNA KCNQ1OT1 and is methylated and inactive on the maternal chromosome. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the Beckwith-Wiedemann Syndrome (BWS) patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Pathogenic variants in KCNQ1 are associated with long-QT syndrome (LQTS) and can be inherited on the paternal or maternal allele. Loss of methylation (LOM) of IC2 has been reported in a small number of individuals with KCNQ1 germline variants which additionally cause LQTS. Valente et al (PMID 30635621) reported three individuals with LQTS, features of BWS and LOM at IC2 and maternally inherited KCNQ1 variants, two of which were demonstrated to affect KCNQ1 transcription upstream of IC2. Essinger et al (PMID 32393365) analysed KCNQ1 in 52 individuals with LOM at IC2 and identified one individual with a splice site variant causing premature transcription termination. Microdeletions of IC2 variably involving KCNQ1, CDKN1C and KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. Maternally inherited LoF variants in CDKN1C are a known cause of BWS. Beygo et al (PMID 30778172) demonstrated that disruption of KCNQ1 prevents methylation of IC2 supporting the hypothesis that transcription of KCNQ1 is required for establishing the maternal methylation imprint at IC2. Sources: Literature |
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| Imprinting disorders v0.13 | KCNQ1OT1 |
Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). ; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Expression is increased in BWS due to IC2 epimutations or paternal UPD. Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). |
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| Imprinting disorders v0.13 | KCNQ1OT1 |
Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C. Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). ; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). |
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| Imprinting disorders v0.13 | KCNQ1OT1 |
Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C. Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). ; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C. Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). |
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| Imprinting disorders v0.13 | KCNQ1OT1 |
Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed. Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879).; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C. Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). |
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| Imprinting disorders v0.13 | KCNQ1 |
Anna Le Fevre gene: KCNQ1 was added gene: KCNQ1 was added to Imprinting disorders. Sources: Literature Mode of inheritance for gene: KCNQ1 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) Publications for gene: KCNQ1 were set to PMID 30635621; 32393365; 30778172 Phenotypes for gene: KCNQ1 were set to Beckwith-Wiedemann Syndrome Penetrance for gene: KCNQ1 were set to unknown Review for gene: KCNQ1 was set to AMBER Added comment: Proposed classification: Amber, pending further evidence. The KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5 is located within KCNQ1 intron 10. IC2 corresponds to the promoter of the long noncoding RNA KCNQ1OT1 and is methylated and inactive on the maternal chromosome. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the Beckwith-Wiedemann Syndrome (BWS) patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Pathogenic variants in KCNQ1 are associated with long-QT syndrome (LQTS) and can be inherited on the paternal or maternal allele. Loss of methylation (LOM) of IC2 has been reported in a small number of individuals with KCNQ1 germline variants which additionally cause LQTS. Valente et al (PMID 30635621) reported three individuals with LQTS, features of BWS and LOM at IC2 and maternally inherited KCNQ1 variants, two of which were demonstrated to affect KCNQ1 transcription upstream of IC2. Essinger et al (PMID 32393365) analysed KCNQ1 in 52 individuals with LOM at IC2 and identified one individual with a splice site variant causing premature transcription termination. Microdeletions of IC2 variably involving KCNQ1, CDKN1C and KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. LoF in CDKN1C is a known cause of BWS. Beygo et al (PMID 30778172) demonstrated that disruption of KCNQ1 prevents methylation of IC2 supporting the hypothesis that transcription of KCNQ1 is required for establishing the maternal methylation imprint at IC2. Sources: Literature |
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| Imprinting disorders v0.13 | KCNQ1OT1 |
Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed. Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LOF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879).; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed. Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879). |
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| Imprinting disorders v0.13 | KCNQ1OT1 |
Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory non-coding RNA KCNQ1OT1 and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed. Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involved neighboring genes KCNQ1 or CDKN1C. LOF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879).; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed. Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LOF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879). |
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| Imprinting disorders v0.13 | KCNQ1OT1 | Anna Le Fevre reviewed gene: KCNQ1OT1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29377879, 10220444, 32447323, 33177595, 29047350; Phenotypes: Growth restriction, Beckwith-Wiedemann Syndrome, Russell-Silver Syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.13 | L3MBTL1 | Anna Le Fevre reviewed gene: L3MBTL1: Rating: RED; Mode of pathogenicity: None; Publications: 23543057; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.13 | ZAR1 |
Anna Le Fevre gene: ZAR1 was added gene: ZAR1 was added to Imprinting disorders. Sources: Literature Mode of inheritance for gene: ZAR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZAR1 were set to 29574422; 31598710; 12539046 Phenotypes for gene: ZAR1 were set to Multi locus imprinting disturbance in offspring Penetrance for gene: ZAR1 were set to unknown Review for gene: ZAR1 was set to AMBER Added comment: Proposed classification: Amber, pending further evidence. Single report of biallelic variants in this gene in a mother of a child with Multi locus imprinting disturbance (MLID) with some features of Beckwith Wiedemann Syndrome. Shown to be a maternal effect gene that functions at the oocyte to embryo transition. Sources: Literature |
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| Imprinting disorders v0.13 | UHRF1 |
Anna Le Fevre gene: UHRF1 was added gene: UHRF1 was added to Imprinting disorders. Sources: Literature Mode of inheritance for gene: UHRF1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UHRF1 were set to 29574422; 28976982 Phenotypes for gene: UHRF1 were set to Multi locus imprinting disturbance in offspring Penetrance for gene: UHRF1 were set to unknown Review for gene: UHRF1 was set to AMBER Added comment: Proposed classification: Amber, pending further evidence. Single report of biallelic variants in this gene in a mother of a child with Multi locus imprinting disturbance (MLID) and Silver Russell Syndrome phenotype. Maenohara et al demonstrate functions of UHRF1 during the global epigenetic reprogramming of oocytes and early embryos. Sources: Literature |
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| Imprinting disorders v0.13 | OOEP |
Anna Le Fevre gene: OOEP was added gene: OOEP was added to Imprinting disorders. Sources: Literature Mode of inheritance for gene: OOEP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OOEP were set to 29574422 Phenotypes for gene: OOEP were set to Multi locus imprinting disturbance in offspring Penetrance for gene: OOEP were set to unknown Review for gene: OOEP was set to AMBER Added comment: Proposed classification: Amber, pending further evidence. Single report of biallelic variants in this gene in a mother of a child with Multi locus imprinting disturbance (MLID) and a transient neonatal diabetes mellitus phenotype. This gene encodes part of the subcortical maternal complex (SCMC). Other genes in this group act as 'maternal effect' genes and are associated with early embryonic arrest, recurrent hydatiform mole and MLID in offspring. As is the case for other genes encoding components of the SCMC, the pathogenicity of variants can be difficult to establish as reproductive outcomes are not recorded in genomic databases and variants may be listed in population databases as they are not classed as pathogenic in males or women with no reproductive history. Functional studies of genes encoding components of the SCMC are limited as their expression is restricted to the oocyte and early embryo. Sources: Literature |
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| Imprinting disorders v0.13 | TLE6 |
Anna Le Fevre gene: TLE6 was added gene: TLE6 was added to Imprinting disorders. Sources: Literature Mode of inheritance for gene: TLE6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TLE6 were set to 26537248; 25542835 Phenotypes for gene: TLE6 were set to Pre-implantation embryonic lethality MIM#616814 Penetrance for gene: TLE6 were set to unknown Review for gene: TLE6 was set to AMBER Added comment: The first report of a single homozygous missense variant in three women from two families with primary infertility was published in 2015. In 2021, Zheng et al reported six biallelic variants in TLE6 in five patients with embryonic arrest, accompanied by direct cleavage and severe fragmentation at the cleavage stage. A mechanism is proposed. I am uncertain regarding classification of this gene (amber vs green) due to the low specificity of this phenotype. I am uncertain if the changes seen in the early embryo, such as fragmentation, make this phenotype more specific. As is the case for other genes encoding components of the subcortical maternal complex (SCMC), the pathogenicity of variants can be difficult to establish as reproductive outcomes are not recorded in genomic databases and variants may be listed in population databases as they are not classed as pathogenic in males or women with no reproductive history. Functional studies of genes encoding components of the SCMC are limited as their expression is restricted to the oocyte and early embryo. Sources: Literature |
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| Imprinting disorders v0.13 | NLRP7 | Anna Le Fevre edited their review of gene: NLRP7: Added comment: There is one report of an individual with recurrent hydatiform mole and biallelic variants in this gene who experienced a single digynic triploid pregnancy presenting as a CHM, whereas other pregnancies were BiCHM (23125094).; Changed publications: 16462743, 28561018, 29574422, 19246479, 22315435, 19066229, 23722513, 23125094 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.13 | KHDC3L |
Anna Le Fevre gene: KHDC3L was added gene: KHDC3L was added to Imprinting disorders. Sources: Literature Mode of inheritance for gene: KHDC3L was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: KHDC3L were set to 23232697; 31847873; 23125094; 21885028 Phenotypes for gene: KHDC3L were set to Hydatiform mold recurrent 2 MIM#614293 Penetrance for gene: KHDC3L were set to unknown Review for gene: KHDC3L was set to GREEN Added comment: Biallelic pathogenic variants in the gene have been associated with Biparental complete hydatifom mole (BiCHM) in multiple individuals. There is one report of an individual with recurrent hydatiform mole and biallelic variants in this gene who experienced a single digynic triploid pregnancy presenting as a CHM, whereas other pregnancies were BiCHM (23125094). Most reported individuals have been found to carry biallelic pathogenic variants in this gene. A minority have been found to carry a heterozygous variant only. A relationship between zygosity and severity of the condition has not been definitively established. As is the case for other genes encoding components of the subcortical maternal complex (SCMC), the pathogenicity of variants can be difficult to establish as reproductive outcomes are not recorded in genomic databases and variants may be listed in population databases as they are not classed as pathogenic in males or women with no reproductive history. Functional studies of genes encoding components of the SCMC are limited as their expression is restricted to the oocyte and early embryo. Sources: Literature |
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| Imprinting disorders v0.13 | NLRP2 | Zornitza Stark Marked gene: NLRP2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.13 | NLRP2 | Zornitza Stark Gene: nlrp2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.13 | NLRP2 | Zornitza Stark Phenotypes for gene: NLRP2 were changed from Beckwith-Wiedemann syndrome due to imprinting defect of 11p15 MONDO:0016475 to Beckwith-Wiedemann syndrome due to imprinting defect of 11p15 MONDO:0016475; Early embryonic arrest; Multi locus imprinting disturbance in offspring | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.12 | NLRP2 | Zornitza Stark reviewed gene: NLRP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.12 | PADI6 | Zornitza Stark Marked gene: PADI6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.12 | PADI6 | Zornitza Stark Gene: padi6 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.12 | PADI6 | Zornitza Stark Mode of inheritance for gene: PADI6 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.11 | NLRP7 | Zornitza Stark Marked gene: NLRP7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.11 | NLRP7 | Zornitza Stark Gene: nlrp7 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.11 | NLRP7 | Zornitza Stark Mode of inheritance for gene: NLRP7 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.10 | NLRP2 | Anna Le Fevre reviewed gene: NLRP2: Rating: ; Mode of pathogenicity: None; Publications: PMID: 30877238, 28317850, 29574422; Phenotypes: Early embryonic arrest, Multi locus imprinting disturbance in offspring; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.10 | PADI6 | Anna Le Fevre reviewed gene: PADI6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29693651, 33583041, 329228291, 33221824, 27545678; Phenotypes: Pre-implantation embryonic lethality 2 MIM#617234, Multi locus imprinting disturbance in offspring, Recurrent hydatiform mole; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.10 | NLRP7 | Anna Le Fevre reviewed gene: NLRP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 16462743, 28561018, 29574422, 19246479, 22315435, 19066229, 23722513; Phenotypes: Biparental complete hydatiform mole, Hydatiform mole, recurrent 1 MIM#231090, Multi locus imprinting disturbance in offspring, reproductive loss; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.10 | NLRP5 | Zornitza Stark Marked gene: NLRP5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.10 | NLRP5 | Zornitza Stark Gene: nlrp5 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.10 | NLRP5 | Zornitza Stark Publications for gene: NLRP5 were set to 26323243; 31201414; 31829238 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.9 | NLRP5 | Zornitza Stark Mode of inheritance for gene: NLRP5 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.8 | NLRP5 |
Anna Le Fevre edited their review of gene: NLRP5: Added comment: Most reported individuals with recurrent early embryonic arrest or mothers of children with MLID have been found to carry biallelic pathogenic variants in this gene. A minority have only been found to carry a heterozygous variant only. A relationship between zygosity and severity of the condition has not been definitively established. As is the case for other genes encoding components of the subcortical maternal complex (SCMC), the pathogenicity of variants can be difficult to establish as reproductive outcomes are not recorded in genomic databases and variants may be listed in population databases as they are not classed as pathogenic in males or women with no reproductive history. Functional studies of genes encoding components of the SCMC are limited as their expression is restricted to the oocyte and early embryo.; Changed phenotypes: Early embryonic arrest, Multi locus imprinting disturbance in offspring |
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| Imprinting disorders v0.8 | ZFP57 | Zornitza Stark Marked gene: ZFP57 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.8 | ZFP57 | Zornitza Stark Gene: zfp57 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.8 | ZFP57 | Zornitza Stark Publications for gene: ZFP57 were set to 18622393; 23150280; 25848000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.7 | MKRN3 | Zornitza Stark reviewed gene: MKRN3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.7 | MKRN3 |
Zornitza Stark Tag SV/CNV tag was added to gene: MKRN3. Tag 5'UTR tag was added to gene: MKRN3. |
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| Imprinting disorders v0.7 | MKRN3 | Zornitza Stark Marked gene: MKRN3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.7 | MKRN3 | Zornitza Stark Gene: mkrn3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.7 | MKRN3 | Zornitza Stark Publications for gene: MKRN3 were set to PMID: 23738509; http://igc.otago.ac.nz/home.html; 30794780 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.6 | KCNK9 | Zornitza Stark Marked gene: KCNK9 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.6 | KCNK9 | Zornitza Stark Gene: kcnk9 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.6 | KCNK9 | Zornitza Stark Phenotypes for gene: KCNK9 were changed from Phenotype resulting from under expression: mental retardation, hypotonia, dysmprophism; Affected tissue: brain; Birk-Barel syndrome to Phenotype resulting from under expression: mental retardation, hypotonia, dysmprophism; Affected tissue: brain; Birk-Barel syndrome, MIM# 612292; MONDO:0012856 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.5 | KCNK9 | Zornitza Stark Publications for gene: KCNK9 were set to http://igc.otago.ac.nz/home.html; PMID: 24667089; 18678320; 30794780 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.4 | KCNK9 | Zornitza Stark reviewed gene: KCNK9: Rating: GREEN; Mode of pathogenicity: None; Publications: 28333430, 27151206, 24980697, 18678320; Phenotypes: Birk-Barel syndrome, MIM# 612292, MONDO:0012856; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.4 | CDKN1C | Zornitza Stark Marked gene: CDKN1C as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.4 | CDKN1C | Zornitza Stark Gene: cdkn1c has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.4 | CDKN1C | Zornitza Stark Publications for gene: CDKN1C were set to 10424811; PMID: 8841187; 22205991]; 20503313; 19843502; http://igc.otago.ac.nz/home.html; [15372379; 23511928; 30794780 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.3 | CDKN1C | Zornitza Stark reviewed gene: CDKN1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 10424811, 8841187, 22205991, 20503313, 19843502, 15372379, 23511928, 30794780, 33076988, 31976094, 31497289; Phenotypes: Beckwith-Wiedemann syndrome, MIM# 130650, IMAGe syndrome, MIM# 614732, Silver-Russell syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.3 | NLRP5 | Anna Le Fevre reviewed gene: NLRP5: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26323243, 31829238, 29574422, 30877238, 32222962, 34440388; Phenotypes: Miscarriage, Beckwith-Wiedemann syndrome, Multi locus imprinting disturbance in offspring; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.3 | ZNF445 |
Anna Le Fevre gene: ZNF445 was added gene: ZNF445 was added to Imprinting disorders. Sources: Literature Mode of inheritance for gene: ZNF445 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF445 were set to PMID: 34039421; 30602440; 30846001 Phenotypes for gene: ZNF445 were set to Temple syndrome; Multi locus imprinting disturbance (MLID) Penetrance for gene: ZNF445 were set to unknown Review for gene: ZNF445 was set to AMBER Added comment: Suggested rating: AMBER Single report (Kagami 2021) of a child with Temple syndrome and MLID found to have a novel homozygous truncating variant in ZNF445. ZNF445 has been shown to play a critical role in the maintenance of postfertilisation methylation imprints (Takahashi 2019). Mechanism and parent of origin effects remain uncertain. Sources: Literature |
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| Imprinting disorders v0.3 | SGCE | Anna Le Fevre reviewed gene: SGCE: Rating: GREEN; Mode of pathogenicity: None; Publications: 11528394, 12325078, 17200151, 16227522, 20301587, 33200041; Phenotypes: myoclonus, dystonia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.3 | UBE3A | Anna Le Fevre reviewed gene: UBE3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 8988171, 16470747; Phenotypes: Angelman syndrome OMIM#105830; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.3 | ZFP57 | Anna Le Fevre reviewed gene: ZFP57: Rating: GREEN; Mode of pathogenicity: None; Publications: 18622393, 27075368, 23150280, 30315371, 31399135, 33053156; Phenotypes: Transient Neonatal Diabetes Mellitus Type 1, Multi Locus Imprinting Disturbance, IUGR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.3 | MKRN3 | Anna Le Fevre reviewed gene: MKRN3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32480405, 33214675, 31041429, 32407292; Phenotypes: Central Precocious Puberty; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.3 | MAGEL2 |
Anna Le Fevre gene: MAGEL2 was added gene: MAGEL2 was added to Imprinting disorders. Sources: Literature Mode of inheritance for gene: MAGEL2 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) Publications for gene: MAGEL2 were set to 24076603; 31397880; 29599419; 30302899 Phenotypes for gene: MAGEL2 were set to Schaaf-Yang syndrome; Chitayat-Hall Syndrome Review for gene: MAGEL2 was set to GREEN Added comment: MAGEL2 is a single-exon gene. Frameshift mutations may not cause nonsense-mediated decay, but instead a variety of truncated or elongated protein products. The pathogenicity of haploinsufficiency of the paternal allele is uncertain (ClinGen review 2018). A dominant-negative effect has been suggested. Haploinsufficiency may play a role. Sources: Literature |
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| Imprinting disorders v0.3 | IGF2 | Zornitza Stark Marked gene: IGF2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.3 | IGF2 | Zornitza Stark Gene: igf2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.3 | IGF2 | Zornitza Stark Phenotypes for gene: IGF2 were changed from Affected tissue: all; Phenotypes resulting from gene over expression: Beckwith-Wiedemann Syndrome (proven effects of dosage alteration rather than gene muation). Phenotype resulting from under expression: Silver-Russell Syndrome to Affected tissue: all; Phenotypes resulting from gene over expression: Beckwith-Wiedemann Syndrome (proven effects of dosage alteration rather than gene muation). Phenotype resulting from under expression: Silver-Russell syndrome 3, MIM #616489 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.2 | IGF2 | Zornitza Stark Publications for gene: IGF2 were set to http://igc.otago.ac.nz/home.html; PMID: 26154720; 30794780 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.1 | IGF2 | Zornitza Stark reviewed gene: IGF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26154720, 31544945; Phenotypes: Silver-Russell syndrome 3, MIM #616489; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.1 | Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Rare Disease | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.0 | ZFP57 |
Zornitza Stark gene: ZFP57 was added gene: ZFP57 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: ZFP57 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZFP57 were set to 18622393; 23150280; 25848000 Phenotypes for gene: ZFP57 were set to IUGR; Diabetes mellitus, transient neonatal 1 OMIM:601410; Multi Locus Imprinting Disturbance; diabetes mellitus, transient neonatal, 1MONDO:0011073 |
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| Imprinting disorders v0.0 | UBE3A |
Zornitza Stark gene: UBE3A was added gene: UBE3A was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: UBE3A was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) Publications for gene: UBE3A were set to 12545427; 8988172; http://igc.otago.ac.nz/home.html; 18500341]; 8988171; 21974935; 2309780; PMID: 9887341; [7795645; 30794780 Phenotypes for gene: UBE3A were set to Affected tissue: brain; Phenotype resulting from under expression: Angelman Syndrome |
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| Imprinting disorders v0.0 | SGCE |
Zornitza Stark gene: SGCE was added gene: SGCE was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: SGCE was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) Publications for gene: SGCE were set to PMID: 25209853; 23237735; 23365103; http://igc.otago.ac.nz/home.html; 30794780 Phenotypes for gene: SGCE were set to Affected tissue: brain; Phenotype resulting from under expression: upper body myoclonus, dystonia |
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| Imprinting disorders v0.0 | PADI6 |
Zornitza Stark gene: PADI6 was added gene: PADI6 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: PADI6 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: PADI6 were set to 27545678; 33221824; 32928291 Phenotypes for gene: PADI6 were set to Preimplantation embryonic lethality 2 OMIM:617234; preimplantation embryonic lethality 2 MONDO:0014978; Multi Locus Imprinting Disturbance; Beckwith-Wiedemann syndrome |
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| Imprinting disorders v0.0 | NLRP7 |
Zornitza Stark gene: NLRP7 was added gene: NLRP7 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: NLRP7 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: NLRP7 were set to 19246479; 28916717; 31201414; 16462743; 29574422 Phenotypes for gene: NLRP7 were set to Affected tissue: all (incompatible with life); hydatidiform mole, recurrent, 1 MONDO:0009273; Phenotype resulting from under expression: Biparental complete hydatidiform mole; Multi Locus Imprinting Disturbance |
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| Imprinting disorders v0.0 | NLRP5 |
Zornitza Stark gene: NLRP5 was added gene: NLRP5 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: NLRP5 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: NLRP5 were set to 26323243; 31201414; 31829238 Phenotypes for gene: NLRP5 were set to Phenotype resulting from under expression: Biparental complete hydatidiform mole, Beckwith-Wiedemann Syndrome, Multi-locus imprinting disorder; Affected tissue: all |
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| Imprinting disorders v0.0 | NLRP2 |
Zornitza Stark gene: NLRP2 was added gene: NLRP2 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: NLRP2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: NLRP2 were set to 26323243; 29574422; 32169557; 28317850; 30221575; 30877238; 33090377; 19300480; 28422141 Phenotypes for gene: NLRP2 were set to Beckwith-Wiedemann syndrome due to imprinting defect of 11p15 MONDO:0016475 Mode of pathogenicity for gene: NLRP2 was set to Other |
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| Imprinting disorders v0.0 | MKRN3 |
Zornitza Stark gene: MKRN3 was added gene: MKRN3 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp 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: 23738509; http://igc.otago.ac.nz/home.html; 30794780 Phenotypes for gene: MKRN3 were set to Phenotype resulting from under expression: Precocious Puberty Syndrome; Affected tissue: HPA axis |
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| Imprinting disorders v0.0 | L3MBTL1 |
Zornitza Stark gene: L3MBTL1 was added gene: L3MBTL1 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: L3MBTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) Publications for gene: L3MBTL1 were set to http://igc.otago.ac.nz/home.html; 23543057; PMID: 15123827; 30794780 Phenotypes for gene: L3MBTL1 were set to Affected tissue: myeloid lineages; Phenotype resulting from under expression: lymphoid malignancy |
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| Imprinting disorders v0.0 | KCNQ1OT1 |
Zornitza Stark gene: KCNQ1OT1 was added gene: KCNQ1OT1 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: KCNQ1OT1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) Publications for gene: KCNQ1OT1 were set to 22205991; 15372379; 10220444; http://igc.otago.ac.nz/home.html; 23511928; 30794780 Phenotypes for gene: KCNQ1OT1 were set to Beckwith-Wiedemann syndrome OMIM:130650 |
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| Imprinting disorders v0.0 | KCNK9 |
Zornitza Stark gene: KCNK9 was added gene: KCNK9 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: KCNK9 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) Publications for gene: KCNK9 were set to http://igc.otago.ac.nz/home.html; PMID: 24667089; 18678320; 30794780 Phenotypes for gene: KCNK9 were set to Phenotype resulting from under expression: mental retardation, hypotonia, dysmprophism; Affected tissue: brain; Birk-Barel syndrome |
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| Imprinting disorders v0.0 | IGF2 |
Zornitza Stark gene: IGF2 was added gene: IGF2 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp 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 http://igc.otago.ac.nz/home.html; PMID: 26154720; 30794780 Phenotypes for gene: IGF2 were set to Affected tissue: all; Phenotypes resulting from gene over expression: Beckwith-Wiedemann Syndrome (proven effects of dosage alteration rather than gene muation). Phenotype resulting from under expression: Silver-Russell Syndrome |
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| Imprinting disorders v0.0 | H19 |
Zornitza Stark gene: H19 was added gene: H19 was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: H19 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) Publications for gene: H19 were set to PMID: 20007505; 15743916; 23118352; [21863054; 21571108; 18245780]; 24916376; 25943194 Phenotypes for gene: H19 were set to Phenotypes resulting from gene over expression: Silver-Russell Syndrome (proven effects of dosage alteration rather than gene muation); Affected tissue: all; Phenotype resulting from under expression: Beckwith-Wiedemann Syndrome |
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| Imprinting disorders v0.0 | GNAS |
Zornitza Stark gene: GNAS was added gene: GNAS was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: GNAS was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) Publications for gene: GNAS were set to 10980525; [11406605; 12024005; 15800843]; 15181091; 9506752; 12024004; http://igc.otago.ac.nz/home.html; 15592469; [15592469; 11788646; 1944469; PMID: 2109828; 30794780 Phenotypes for gene: GNAS were set to Affected tissue: kidney, bone, brain; pseudopseudohypoparathyroidism; Phenotype resulting from under expression: Pseudohypoparathyroidism Type 1a |
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| Imprinting disorders v0.0 | CDKN1C |
Zornitza Stark gene: CDKN1C was added gene: CDKN1C was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: CDKN1C was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) Publications for gene: CDKN1C were set to 10424811; PMID: 8841187; 22205991]; 20503313; 19843502; http://igc.otago.ac.nz/home.html; [15372379; 23511928; 30794780 Phenotypes for gene: CDKN1C were set to Affected tissue: all; Phenotype resulting from under expression: Beckwith-Wiedemann Syndrome; Phenotypes resulting from gene over expression: IMAGE syndrome; Silver-Russell Syndrome |
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| Imprinting disorders v0.0 | Zornitza Stark Added panel Imprinting disorders | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||