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| Fetal anomalies v0.4686 | PRIM1 |
Belinda Chong gene: PRIM1 was added gene: PRIM1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: PRIM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRIM1 were set to 33060134 Phenotypes for gene: PRIM1 were set to Microcephalic primordial dwarfism, MONDO:0017950 Review for gene: PRIM1 was set to AMBER gene: PRIM1 was marked as current diagnostic Added comment: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant. Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD). Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinaemia, and lymphopaenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections. Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype. Sources: Literature |
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| Fetal anomalies v0.4572 | PIK3R1 | Zornitza Stark Phenotypes for gene: PIK3R1 were changed from AGAMMAGLOBULINEMIA 7, AUTOSOMAL RECESSIVE; SHORT SYNDROME to SHORT syndrome, MIM#269880 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3366 | LRBA | Zornitza Stark Phenotypes for gene: LRBA were changed from CHILDHOOD-ONSET HYPOGAMMAGLOBULINEMIA to Immunodeficiency, common variable, 8, with autoimmunity MIM#614700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3279 | ZBTB24 |
Krithika Murali gene: ZBTB24 was added gene: ZBTB24 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ZBTB24 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZBTB24 were set to 32865561; 21596365; 29023266; 32061411; 21906047; 28128455; 23739126; 22786748 Phenotypes for gene: ZBTB24 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 2 - MIM#614069 Review for gene: ZBTB24 was set to GREEN Added comment: Well reported association with ICF2 (immunodeficiency-centromeric instability facial anomalies syndrome 2). Patients have immunodeficiency (mainly hypo/agammaglobulinemia in the presence of B cells), recurrent infections (namely respiratory and gastrointestinal) and dysmorphic facies. Although antenatal features not thoroughly described for published cases, low birth weight has been a reported feature as well as hypertelorism and micrognathia/retrognathia - these have the potential to be detected prenatally. PMID 32865561 Helfricht et al 2020 - "loss of ZBTB24 in B cells from mice and ICF2 patients affects nonhomologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and isotype balance". PMID 32061411 Banday. et al 2020 - report a patient with this condition and granulomatous hepatitis. Review phenotype of previously reported patients, low birth weight and facial dysmorphism including micrognathia noted in other cases. PMID 29023266 Conrad et al 2017 - describe a 17 month old boy with recurrent infections, growth failure, facial anomalies (including hyperterlorism/low set ears), and inflammatory bowel disease. No antenatal information. PMID 28128455 van den Boogaard 2017 - 5 new patients described PMID 23739126 Nitta et al 2013 - report 3 unrelated patients, x1 patient - lower birth weight and head circumference. At age 5 had macrocephaly, hyperterlorism. Noted to have bilateral hydronephrosis. x1 patient BW 2660g, micrognathia, hyperterlorism. PMID 21906047 Chouery et al 2012 - 3 siblings from a Lebanese family with novel homozygous LoF variant. Apparently normal pregnancies, at time of diagnostic assessment HC between the 5th and 15th centiles, height below the 5th percentile. Dysmorphic features including high arched palate, small chin, retrognathism and everted lower lips. PMID 22786748 Cerbone et al 2012 - report an 8 year old M of consanguineous Moroccan ancestry with ID, dysmorphic features, cafe au last macules and a large arachnoid cyst in the right temporal region, causing compression of the temporal lobe and lateral ventricle PMID 21596365 de Greef et al 2011 - report 4 new unrelated patients, no antenatal information Sources: Literature |
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| Fetal anomalies v0.2715 | NAGLU | Zornitza Stark Marked gene: NAGLU as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2715 | NAGLU | Zornitza Stark Gene: naglu has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2715 | NAGLU | Zornitza Stark Phenotypes for gene: NAGLU were changed from MUCOPOLYSACCHARIDOSIS TYPE 3B to Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2714 | NAGLU | Zornitza Stark Publications for gene: NAGLU were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2713 | NAGLU | Zornitza Stark Classified gene: NAGLU as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2713 | NAGLU | Zornitza Stark Gene: naglu has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2712 | NAGLU | Zornitza Stark reviewed gene: NAGLU: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.2665 | NAGLU | Ain Roesley reviewed gene: NAGLU: Rating: AMBER; Mode of pathogenicity: None; Publications: 8650226; Phenotypes: Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1469 | SPEN |
Krithika Murali gene: SPEN was added gene: SPEN was added to Fetal anomalies. Sources: Expert list,Literature Mode of inheritance for gene: SPEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPEN were set to 33596411 Phenotypes for gene: SPEN were set to Radio-Tartaglia syndrome - MIM#619312 Review for gene: SPEN was set to GREEN Added comment: Radio et al. (2021) reported heterozygous SPEN variants in 34 individuals from 33 unrelated families with had global developmental delay, ID, behavioural issues and dysmorphic features. Other features included hypotonia, gait imbalance, pyramidal signs and seizures. Findings potentially ascertainable antenatally: - Brain imaging abnormalities include polymicrogyria, heterotopia, cerebellar atrophy, periventricular white matter defects, agenesis of the corpus callosum, and tethered cord. - Congenital heart defects also present in a significant proportion. Sources: Expert list, Literature |
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| Fetal anomalies v0.915 | PRRX1 |
Zornitza Stark gene: PRRX1 was added gene: PRRX1 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: PRRX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PRRX1 were set to 21294718; 22211708; 22674740; 23444262 Phenotypes for gene: PRRX1 were set to Agnathia-otocephaly complex, MIM# 202650 Review for gene: PRRX1 was set to GREEN Added comment: Agnathia-otocephaly is a rare condition characterized by mandibular hypoplasia or agnathia, ventromedial auricular malposition (melotia) and/or auricular fusion (synotia), and microstomia with oroglossal hypoplasia or aglossia. Holoprosencephaly is the most commonly identified association, but skeletal, genitourinary, and cardiovascular anomalies, and situs inversus have been reported. The disorder is almost always lethal. Three unrelated individuals reported with heterozygous LoF variants, one family with bi-allelic variants. Sources: Expert Review |
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| Fetal anomalies v0.87 | AGL | Zornitza Stark Marked gene: AGL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.87 | AGL | Zornitza Stark Gene: agl has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.87 | AGL | Zornitza Stark Phenotypes for gene: AGL were changed from GLYCOGEN STORAGE DISEASE TYPE III to Glycogen storage disease IIIa, MIM# 232400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.86 | AGL | Zornitza Stark Classified gene: AGL as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.86 | AGL | Zornitza Stark Gene: agl has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.85 | AGL | Zornitza Stark changed review comment from: Presentation is typically with muscle, liver and cardiac involvement.; to: Presentation is typically with muscle, liver and cardiac involvement, can be childhood, but many are in adulthood. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | NAGLU |
Zornitza Stark gene: NAGLU was added gene: NAGLU was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: NAGLU was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NAGLU were set to MUCOPOLYSACCHARIDOSIS TYPE 3B |
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| Fetal anomalies v0.0 | LRBA |
Zornitza Stark gene: LRBA was added gene: LRBA was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: LRBA was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: LRBA were set to CHILDHOOD-ONSET HYPOGAMMAGLOBULINEMIA |
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| Fetal anomalies v0.0 | PIK3R1 |
Zornitza Stark gene: PIK3R1 was added gene: PIK3R1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: PIK3R1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: PIK3R1 were set to AGAMMAGLOBULINEMIA 7, AUTOSOMAL RECESSIVE; SHORT SYNDROME |
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| Fetal anomalies v0.0 | AGL |
Zornitza Stark gene: AGL was added gene: AGL was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: AGL was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: AGL were set to GLYCOGEN STORAGE DISEASE TYPE III |
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