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| Mendeliome v1.4288 | GAL |
Bryony Thompson gene: GAL was added gene: GAL was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GAL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GAL were set to 25691535 Phenotypes for gene: GAL were set to familial temporal lobe epilepsy 8 MONDO:0014650 Review for gene: GAL was set to RED Added comment: 2 monozygotic male twins with familial temporal lobe epilepsy with a de novo heterozygous missense variant (p.A39E). In vitro functional assay showed antagonistic activity against galanin receptor 1 (GalR1)-mediated response, and decreased binding affinity and reduced agonist properties for GalR2. Sources: Literature |
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| Mendeliome v1.4017 | TMEM251 |
Zornitza Stark edited their review of gene: TMEM251: Added comment: PMID 40171858: reports 2 siblings from an Iranian consanguineous family and six previously reported families (8 patients, 7 unrelated families) with biallelic loss‑of‑function LYSET variants presenting with MLII‑like mucolipidosis; core features include dysostosis multiplex, coarse facial features, hepatomegaly, joint contractures, developmental delay; mouse knockout recapitulates the phenotype, supporting gene‑disease causality. HGNC approved name is LYSET.; Changed rating: GREEN; Changed publications: 40171858 |
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| Mendeliome v1.3732 | TBXAS1 | Zornitza Stark edited their review of gene: TBXAS1: Added comment: PMID 27156553, 28868793, 33244729, 33595912, 36786374, 39220787 and 39277773 together report 10 individuals from 8 unrelated families with biallelic loss‑of‑function variants in TBXAS1. Clinical features include anemia/pancytopenia, thrombocytopenia, bone‑marrow fibrosis, splenomegaly and markedly increased diaphyseal bone density, often responding to steroids.; Changed publications: 18264100, 27156553, 28868793, 33244729, 33595912, 36786374, 39220787, 39277773 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3649 | Zornitza Stark Added reviews for gene C1GALT1C1 from panel Atypical Haemolytic Uraemic Syndrome_MPGN | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3646 | A4GALT | Zornitza Stark Phenotypes for gene: A4GALT were changed from [Blood group, P1Pk system, p phenotype], MIM# 111400 to A4GALT-congenital disorder of glycosylation MONDO:0100587 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3645 | A4GALT | Zornitza Stark Publications for gene: A4GALT were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3644 | A4GALT | Zornitza Stark Mode of inheritance for gene: A4GALT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3643 | A4GALT | Zornitza Stark Classified gene: A4GALT as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3643 | A4GALT | Zornitza Stark Gene: a4galt has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3518 | CTSA | Zornitza Stark Phenotypes for gene: CTSA were changed from Galactosialidosis, MIM# 256540; Cathepsin A-related arteriopathy with strokes and leukoencephalopathy to Galactosialidosis, MIM# 256540; Brain small vessel disease 6 with leukoencephalopathy, MIM# 621394 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3517 | CTSA | Zornitza Stark edited their review of gene: CTSA: Changed phenotypes: Galactosialidosis, MIM# 256540, Brain small vessel disease 6 with leukoencephalopathy, MIM# 621394 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3406 | ABCB4 |
Chirag Patel Source Victorian Clinical Genetics Services was removed from ABCB4. Phenotypes for gene: ABCB4 were changed from Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism; Gallbladder disease 1 (MIM#600803) to Progressive familial intrahepatic cholestasis type 3, MONDO:0011214; Cholestasis, intrahepatic, of pregnancy, 3 MIM#614972; disorder of bile acid metabolism; Gallbladder disease 1 (MIM#600803) |
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| Mendeliome v1.3362 | RNU6ATAC |
Lucy Spencer gene: RNU6ATAC was added gene: RNU6ATAC was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNU6ATAC were set to 40975062 Phenotypes for gene: RNU6ATAC were set to Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related Review for gene: RNU6ATAC was set to RED Added comment: PMID: 40975062 1 patient compound heterozygous for n.36T>G and n.28C>T. Has short stature, microcephaly, hypotonia, neurodevelopmental delay, ID, seizures, ataxia, ventriculomegaly, syndactyly, nystagmus and oculomotor apraxia. Identified in a cohort of individuals with an excess of significant intron retention outliers in minor intron containing genes which are usually removed by the minor spliceosome of which RNU6ATAC is a part (as is RNU4ATAC). Proband had no candidate variants in RNU4ATAC or RNU12. Both RNU6ATAC variants are in a highly conserved 39bp region, and affect nucleotides predicted to be important for binding to U4ATAC. Sources: Literature |
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| Mendeliome v1.3268 | RAG1 | Zornitza Stark Phenotypes for gene: RAG1 were changed from Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889; Combined cellular and humoral immune defects with granulomas MIM# 233650; Omenn syndrome MIM# 603554; Severe combined immunodeficiency, B cell-negative MIM# 601457 to Recombinase activating gene 1 deficiency MONDO:0000572 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3113 | SNAPIN |
Lucy Spencer gene: SNAPIN was added gene: SNAPIN was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SNAPIN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SNAPIN were set to 40930097; 26539891 Phenotypes for gene: SNAPIN were set to Neurodevelopmental disorder (MONDO:0700092), SNAPIN-related Review for gene: SNAPIN was set to GREEN Added comment: PMID: 40930097 6 patients from 5 families with neuroanatomical, craniofacial, and skeletal anomalies on prenatal ultrasound/MRI, all homozygous for variants in SNAPIN. 2 stopgain, 1 canonical splice, 5 missense. common phenotypes: ventriculomegaly 5/6, cerebellar hypoplasia/atrophy 5/6, clubfeet 4/6, corpus callosum agenesis 4/6, flexion contractures 4/6, microcephaly 3/6, micrognathia/retrognathia 4/6. The patients with the nonsense or splice variants did not survive the perinatal period, while those with missense survived into early childhood. This paper also mentions a 7th patient reported in PMID: 26539891, who has ID, microcephaly, cortical atrophy, bulbar and cerebellar hypoplasia, sensorineural polyneuropathy, and hypotonia. They are homozygous for a missense variant Asn55Tyr. Of note, the other paper report this as Arg55Trp and one of their patients also has this variant, based off the transcript information provided in both papers Arg55Trp is correct. PMID: 40930097 Knockout zebrafish models recapitulated the human phenotype. This phenotype was rescued by injecting WT human SNAPIN RNA. Injection with the 2 missense variants observed in patients in this study was able to partially rescue the phenotype but it was significantly worse than the rescue with WT injection. One of these missense variants is absent from gnomad (Arg55Trp) while the other (Glu49Asp) has 167 hets and 1 hom. Sources: Literature |
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| Mendeliome v1.2825 | RC3H1 |
Zornitza Stark edited their review of gene: RC3H1: Added comment: PMID 40769319: 3 individuals (heterozygous c.T674C (p.F225S)) from an extended kindred presenting with a spectrum of infections, lymphoproliferation, and autoimmune manifestations (upper respiratory infections, otitis media, sinusitis, abscess formation, pneumonia, and bacteremia, psoriasis, cytopenias, and liver disease. hyper-inflammation and lymphoproliferation manifesting with exaggerated generalized lymphadenopathy and splenomegaly. Transfected cell model provided functional support. RED for mono-allelic association, single family.; Changed publications: 31636267, 15917799, 40769319; Changed phenotypes: Hemophagocytic lymphohistiocytosis, familial, 6, MIM# 618998 |
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| Mendeliome v1.2810 | CHTF18 |
Sangavi Sivagnanasundram gene: CHTF18 was added gene: CHTF18 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CHTF18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CHTF18 were set to 40717333 Phenotypes for gene: CHTF18 were set to complex neurodevelopmental disorder with or without congenital anomalies (Cohesinopathies) MONDO:0100465 Review for gene: CHTF18 was set to GREEN Added comment: >5 unrelated individuals with a rare missense variant in the gene have been identified by the authors however the clinical details were presented on three. 3 different de novo missense variants were identified 3 individuals - neurodevelopment delay, epilepsy, de novo: 1 - 9M with DD, autism and seizures. De novo variant identified - p.Leu355Val 2 - 23month F with congenital bilateral ventriculomegaly status post ventriculoperitoneal shunt placement, epilepsy, right eye optic nerve hypoplasia, hypotonic cerebral palsy complicated by left hip subluxation, and G-tube dependence. De novo variant identified - p.His645Pro 3 - 3F presenting with global DD, hypotonia, seizure and abnormal brain MRI. De novo variant identified - p.Leu676Arg Sources: Literature |
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| Mendeliome v1.2748 | CDC25A |
Zornitza Stark gene: CDC25A was added gene: CDC25A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: CDC25A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CDC25A were set to 40342881; 30009144; 16720623 Phenotypes for gene: CDC25A were set to Spermatogenic failure, MONDO:0004983, CDC25A-related Review for gene: CDC25A was set to GREEN Added comment: i) PMID: 40342881- Five novel heterozygous variants (Lys500Asn in 8 cases, His459Leu in 12 cases, Ser485Asp, Thr503Ser, c.1434 + 5G>C) and one previously identified SNP (in 7 cases) in azoospermic males from the Bengali-speaking Indian population. qPCR analysis indicated downregulation of CDC25A mRNA expression in azoospermic patients relative to fertile controls. Relative expression levels of CDC25A were about 2.5-fold lower in azoospermic testicular tissue and semen samples, reflecting diminished transcriptional activity in affected patients. This reduction in gene expression may reflect a potential functional deficiency of CDC25A, contributing to spermatogenic arrest. The decreased level of CDC25A mRNA levels corresponds with the findings of pathogenic variants identified in azoospermic patients, thus solidifying the evidence of CDC25A mutations contributing to male infertility. ii) PMID: 30009144,16720623- decreased expression of CDC25A observed in testicular biopsies from azoospermic men, suggesting association with meiotic arrest as the etiology of spermatogenic failure. Sources: Literature |
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| Mendeliome v1.2706 | GALM | Bryony Thompson Phenotypes for gene: GALM were changed from galactosaemia; type IV galactosaemia to galactosaemia; type IV galactosaemia MONDO:0030105 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2653 | A4GALT | Sangavi Sivagnanasundram reviewed gene: A4GALT: Rating: GREEN; Mode of pathogenicity: None; Publications: 12823750, 15142124, 10747952, 10993874, 11896312, 27612185; Phenotypes: A4GALT-congenital disorder of glycosylation MONDO:0100587; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2624 | GALNT14 | Zornitza Stark Marked gene: GALNT14 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2624 | GALNT14 | Zornitza Stark Gene: galnt14 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2624 | GALNT14 |
Zornitza Stark gene: GALNT14 was added gene: GALNT14 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GALNT14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GALNT14 were set to 40153534 Phenotypes for gene: GALNT14 were set to IgA Nephropathy, susceptibility to, MONDO:0100555, GALNT14-related Review for gene: GALNT14 was set to RED Added comment: LoF variant identified in large pedigree, including 6 affected individuals. Also found in 3 unaffected relatives. Supportive mouse model. Sources: Literature |
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| Mendeliome v1.2550 | KEL | Zornitza Stark Phenotypes for gene: KEL were changed from [Blood group, Kell] 110900 to vein of Galen aneurysm, MONDO:0015196 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2547 | KEL | Zornitza Stark reviewed gene: KEL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: vein of Galen aneurysm, MONDO:0015196; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2499 | KEL | Achchuthan Shanmugasundram reviewed gene: KEL: Rating: AMBER; Mode of pathogenicity: None; Publications: 30578106, 37978175; Phenotypes: vein of Galen aneurysm, MONDO:0015196; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2479 | B3GALT6 | Sangavi Sivagnanasundram reviewed gene: B3GALT6: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008674; Phenotypes: B3GALT6-congenital disorder of glycosylation MONDO:0100586; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2400 | SVBP | Zornitza Stark edited their review of gene: SVBP: Added comment: PMID 39412222: 6 individuals from 3 families with spastic paraplegia and the same homozygous missense (L49P). Presented from birth or childhood with DD/ID and spastic paraplegia. Additional features: verbal apraxia, axonal neuropathy, ataxia, nystagmus, epilepsy, and aggressive behaviour. Brain MRIs were performed in 3 individuals and showed thinning of the corpus callosum, cerebellar atrophy, and ventriculomegaly; frontal ventricular hyperintensities suggestive of the 'ear of the lynx' sign in 2. Three individuals had a history of cancer of epithelial origin, including adenocarcinoma (patient 1), colonic tubular adenoma (patient 2), and breast cancer (patient 3).; Changed publications: 31363758, 30607023, 39412222; Changed phenotypes: Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, MIM #618569, Spastic paraplegia 94, autosomal recessive, MIM# 621150 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2274 | PPA1 |
Zornitza Stark gene: PPA1 was added gene: PPA1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PPA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPA1 were set to 37999237 Phenotypes for gene: PPA1 were set to Galactosaemia, MONDO:0018116 Review for gene: PPA1 was set to RED Added comment: Homozygous missense variant detected in two siblings with increased galactose and galactose-related metabolites ascertained in neonatal screening. Some supportive functional data. Sources: Literature |
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| Mendeliome v1.2236 | LDB1 |
Bryony Thompson gene: LDB1 was added gene: LDB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: LDB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LDB1 were set to 39680505 Phenotypes for gene: LDB1 were set to Congenital hydrocephalus MONDO:0016349 Review for gene: LDB1 was set to GREEN Added comment: Exome-wide significant enrichment of LDB1 protein-altering de novo variants (p = 1.11 x 10-15) in a large cerebral ventriculomegaly cohort (>2,697 parent-proband trios). 8 unrelated cases with ventriculomegaly, developmental delay, and dysmorphic features with de novo variants (7 LoF variants truncate LDB1's carboxy-terminal LIM interaction domain & 1 missense). Sources: Literature |
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| Mendeliome v1.2191 | TCP1 |
Ain Roesley gene: TCP1 was added gene: TCP1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TCP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TCP1 were set to 39480921 Phenotypes for gene: TCP1 were set to neurodevelopmental disorder MONDO:0700092, TCP1-related Penetrance for gene: TCP1 were set to Complete Review for gene: TCP1 was set to GREEN gene: TCP1 was marked as current diagnostic Added comment: previously known as CCT1 8x individuals including 5x de novo 6x PTCs + 2x missense 6/8 DD/ID 2/8 visual impairment 6/8 seizures 6/8 polymicrogyria + 1x Ventriculomegaly, white matter hyperintensities Sources: Literature |
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| Mendeliome v1.2089 | IRAK2 |
Chirag Patel changed review comment from: 2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria. Individual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported. Individual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported. Both patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens). Paper does not comment on reasons for disease in biallelic and mono-allelic form. Sources: Literature; to: PMID: 39299377 2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria. Individual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported. Individual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported. Both patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens). Paper does not comment on reasons for disease in biallelic and mono-allelic form. Preprint paper: 2 individuals with immune dysregulation (1 x systemic lupus erythematosus and 1 x autoinflammatory disease) with same homozgyous exon 2 deletion in IRAK2 gene found on WES testing and confirmed with Sanger sequencing. Unaffected family members in trio were heterozygous for variant. Exon 2 encodes a proportion of the death domain, a critical protein domain for Myddosome assembly. The patients exhibited aberrantly upregulated type I interferon (IFN) response following LPS stimulation, which was further confirmed in bone marrow-derived macrophages (BMDMs) in mice. RNA sequencing analysis indicated that PBMCs from the two patients consistently exhibited defects in activating NFkb signaling in response to LPS or R848 stimulation, as well as impaired activation of the MAPK signaling pathway. RNA sequencing demonstrated that BMDMs from Irak2 ∆ex2/∆ex2 mice exhibited defects in NFkb and MAPK signaling pathways, similar to patients’ PBMCs. |
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| Mendeliome v1.2089 | IRAK2 |
Chirag Patel gene: IRAK2 was added gene: IRAK2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IRAK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: IRAK2 were set to PMID: 39299377 Phenotypes for gene: IRAK2 were set to Immunodeficiency, no OMIM # Review for gene: IRAK2 was set to RED Added comment: 2 individuals with sequential or repeated invasive infections with 2 different variants in IRAK2 gene found on WES testing. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. IRAK4 gene has been associated with susceptibility to severe infections by common pyogenic bacteria. Individual 1 had herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and a homozygous missense variant (L78P). There are no homozygous individuals in gnomAD (MAF 0.003%). No segregation testing reported. Individual 2 had Streptococcus pneumoniae bacteremia with candidemia, and a heterozygous missense variant (R506W) which straddles between the kinase and TRAF6-binding CTD of IRAK2. There are 15 heterozygous individuals in gnomAD for this rare variant with no homozygotes (MAF 0.012%). No segregation testing reported. Both patients’ peripheral blood mononuclear cells showed tendencies for TNFα hypo-responsiveness to representative bacterial, fungal and viral ligands, in line with subjects with IRAK defects. Immunoprecipitation platform assay to pull down TRAF6 revealed that possession of L78P or R506W variants led to reduced TRAF6 ubiquitination. The led to TRAF6 accumulation and in turn decreased TNFα production (an inflammatory cytokine to invading pathogens). Paper does not comment on reasons for disease in biallelic and mono-allelic form. Sources: Literature |
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| Mendeliome v1.1998 | MRPL42 |
Mark Cleghorn gene: MRPL42 was added gene: MRPL42 was added to Mendeliome. Sources: Other Mode of inheritance for gene: MRPL42 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MRPL42 were set to complex neurodevelopmental disorder MONDO:0100038 Penetrance for gene: MRPL42 were set to unknown Review for gene: MRPL42 was set to RED Added comment: Bjorn Fischer-Zirnsak, Charite Berlin ESHG presentation 4/6/24, unpublished ++ supportive functional data (on patient-derived cells) presented, but only 1 case Biallelic MRPL42 LoF with lethal mitochondrial disease Index case, born to consanguineous parents Small Hypotonia Seizures Conductive hearing impairment CV: hypertrophic RV, small VSD Hepatomegaly Lactic acidosis Homozygous MRPL42: c.219+6T>A (spliceAI 0.83 donor loss) RNASeq and RT-PCR supportive of aberrant splicing resulting in out of frame exon 4 skipping Sources: Other |
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| Mendeliome v1.1860 | VPS50 |
Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene. Sanger confirmed the Lys5* to be 'homozygous' in the proband. Phenotypes include: microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene. Sanger confirmed the Lys5* to be 'homozygous' in the proband. Phenotypes include: severe ID, muscular hypotonia, sensorineural hearing impairment, microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive |
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| Mendeliome v1.1855 | VPS50 |
Ain Roesley changed review comment from: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene. Sanger confirmed the Lys5* to be 'homozygous' in the proband. Phenotypes include: nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive; to: 1x proband Chet for a nonsense p.(Lys5*) and a complex structural variant of a 4.3Mb inversion, flanked by 170kb and 428kb deletions, respectively. The 428kb deletion spans the entire VPS50 gene. Sanger confirmed the Lys5* to be 'homozygous' in the proband. Phenotypes include: microcephaly, nystagmus, seizures, hypoplastic corpus callous, neonatal low GGT cholesatsis, hepatomegaly, failure to thrive |
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| Mendeliome v1.1685 | GALE | Zornitza Stark Phenotypes for gene: GALE were changed from Galactose epimerase deficiency MIM#230350; Disorders of galactose metabolism to Galactose epimerase deficiency MIM#230350; Thrombocytopenia 12, syndromic, MIM#620776 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1684 | GALE | Zornitza Stark Publications for gene: GALE were set to 27604308; 9700591 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1683 | GALE | Zornitza Stark reviewed gene: GALE: Rating: GREEN; Mode of pathogenicity: None; Publications: 30247636, 34159722, 36395340; Phenotypes: Thrombocytopenia 12, syndromic, MIM#620776; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1417 | SLC19A1 | Zornitza Stark Phenotypes for gene: SLC19A1 were changed from Megaloblastic anemia, folate-responsive, MIM# 601775 to Megaloblastic anemia, folate-responsive, MIM# 601775; Combined immunodeficiency, SLC19A1-related MONDO:0015131 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1390 | FA2H |
Zornitza Stark changed review comment from: Well established gene-disease association, both peripheral and central features (dystonia, dysarthria, cognitive impairment, and epilepsy), childhood-onset, progressive. Sources: Expert Review; to: Well established gene-disease association, both peripheral and central features (dystonia, dysarthria, cognitive impairment, and epilepsy), childhood-onset, progressive. PubMed: 31135052 – 19 patients from 16 families consistent with a complicated form of SPG. PubMed:18463364 – 7 individuals identified from a large consanguineous family with SPG. PubMed: 19068277 – 7 patients from 2 unrelated consanguineous middle eastern families PubMed: 20104589– Multiple affected individuals in an Omani family. Findings indicated that an abnormal hydroxylation of myelin galactocerebroside lipid components can lead to the progression of a severe phenotype. Sources: Expert Review |
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| Mendeliome v1.1376 | ARPC5 | Zornitza Stark commented on gene: ARPC5: Features of autoinflammation common: haemolytic anaemia, thrombocytopenia, hepatosplenomegaly, leukocytosis, neutrophilia, and elevated acute phase reactants. More variable systemic features may include coeliac disease or enteropathy, ileus, nephropathy, eczema, and dermatomyositis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1362 | THOC6 | Ling Sun reviewed gene: THOC6: Rating: AMBER; Mode of pathogenicity: None; Publications: 35426486, 30476144; Phenotypes: VSD/ASD, severe aortic and left ventricular hypoplasia, Mild dilation of the right chambers and a mild myocardial hypertrophy secondary to a chronic hypertension, ventriculomegaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1262 | MYCN | Elena Savva Phenotypes for gene: MYCN were changed from Feingold syndrome 1; megalencephaly; ventriculomegaly; hypoplastic corpus callosum; intellectual disability; polydactyly; neuroblastoma to Neurodevelopmental disorder (MONDO:0700092), MYCN-related; Feingold syndrome 1 MIM#164280 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1231 | CSGALNACT1 | Zornitza Stark Phenotypes for gene: CSGALNACT1 were changed from Congenital disorders of glycosylation; skeletal dysplasia; advanced bone age to Skeletal dysplasia, mild, with joint laxity and advanced bone age, MIM# 618870 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1230 | CSGALNACT1 | Zornitza Stark edited their review of gene: CSGALNACT1: Changed phenotypes: Skeletal dysplasia, mild, with joint laxity and advanced bone age, MIM# 618870 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1077 | AQP4 | Zornitza Stark Phenotypes for gene: AQP4 were changed from ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 to Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1071 | AQP4 |
Lucy Spencer gene: AQP4 was added gene: AQP4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AQP4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AQP4 were set to 37143309 Phenotypes for gene: AQP4 were set to ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 Review for gene: AQP4 was set to AMBER Added comment: PMID: 37143309 Cohort of patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). Missense variant in AQP4 seen homozygous in 2 siblings and het in the parents. Patients had macrocephaly, developmental delay, hypotonia, epilepsy, and cognitive deficit. Western blots on generated MDCK cell lines showed no detectable expression of AQP4 protein from the cells with the patients variant. Immunofluorescence also showed no membrane expression. Overexpression studies in HEK293T cells showed WT was seen as mainly monomers or dimers where as variant protein formed large aggregates- likely due to the saturation of protein degradation pathways because of the overexpression. Sources: Literature |
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| Mendeliome v1.1071 | GPRC5B |
Lucy Spencer gene: GPRC5B was added gene: GPRC5B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GPRC5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GPRC5B were set to 37143309 Phenotypes for gene: GPRC5B were set to Megalencephalic leukoencephalopathy with subcortical cysts 3 620447 Review for gene: GPRC5B was set to GREEN Added comment: PMID: 37143309 Cohort of 5 patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). 3 unrelated patients had variants in GPRC5B, 2 have the same inframe dup Ile175dup and the third has an in frame dup of Ala177. All 3 were de novo and unaffected siblings did not have the variants. All patients have macrocephaly, delayed motor development, seizures, all had varying degrees of cognitive deficits. 2 also had spasticity, ataxia and dystonia. MRI showed MLC, abnormal and swollen cerebral white matter. Patient cell lines showed reduced regulatory volume decrease, and western blot showed a strong increase in GRPC5B levels in patient lymphoblasts. Together, these findings indicate disturbed volume regulation in lymphoblasts from patients with GPRC5B variants, potentially due to increased GPRC5B levels. Transfected cells caused increased volume-regulated anion channel activity. Sources: Literature |
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| Mendeliome v1.1054 | STX5 |
Ain Roesley gene: STX5 was added gene: STX5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: STX5 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: STX5 were set to congenital disorder of glycosylation MONDO#0015286, STX5-related Review for gene: STX5 was set to AMBER gene: STX5 was marked as current diagnostic Added comment: 1x family with 3x deceased shortly after death + 3x spontaneous abortions + 2x abortions due to abnormal fatal ultrasound (US). Hom for NM_003164.4:c.163 A > G p.(Met55Val), which results in complete loss of short isoform (which uses Met55 as the start) phenotype: short long bones on US, dysmorphism, skeletal dysplasia, profound hypotonia, hepatomegaly elevated cholesterol. Post-natally they died of progressive liver failure with cholestasis and hyperinsulinemic hypoglycemias Primary human dermal fibroblasts isolated from these patients show defective glycosylation, altered Golgi morphology as measured by electron microscopy, mislocalization of glycosyltransferases, and compromised ER-Golgi trafficking Sources: Literature |
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| Mendeliome v1.972 | C1GALT1C1 | Zornitza Stark commented on gene: C1GALT1C1: Two maternal half-brothers with missense variant and aHUS phenotype reported, increasing evidence for association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.972 | C1GALT1C1 | Zornitza Stark reviewed gene: C1GALT1C1: Rating: AMBER; Mode of pathogenicity: None; Publications: 37216524; Phenotypes: Haemolytic uraemic syndrome, atypical, 8, with rhizomelic short stature, MIM# 301110; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.775 | ESAM |
Chern Lim gene: ESAM was added gene: ESAM was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ESAM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ESAM were set to 36996813 Phenotypes for gene: ESAM were set to Neurodevelopmental disorder (MONDO#0700092), ESAM-related Review for gene: ESAM was set to GREEN gene: ESAM was marked as current diagnostic Added comment: PMID 36996813 - Thirteen affected individuals, including four fetuses, from eight unrelated families, with homozygous loss-of-function-type variants in ESAM – 2 of the variants are frameshifts, 1x nonsense, 1x canonical splice. - Affected individuals have profound global developmental delay/unspecified intellectual disability, epilepsy, absent or severely delayed speech, varying degrees of spasticity, ventriculomegaly, and ICH/cerebral calcifications, the latter being also observed in the fetuses. - One of the frameshift variant c.115del (p.Arg39Glyfs*33), was detected in six individuals from four unrelated families from the same geographic region in Turkey (southeastern Anatolia), suggesting a founder effect. - The c.451+1G>A variant was detected in three individuals from two independent families with the same ethnic origin (Arab Bedouin) Sources: Literature |
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| Mendeliome v1.717 | RBSN |
Zornitza Stark gene: RBSN was added gene: RBSN was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RBSN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RBSN were set to 25233840; 29784638; 35652444 Phenotypes for gene: RBSN were set to intellectual disability, MONDO:0001071, RBSN-related Review for gene: RBSN was set to GREEN Added comment: Four unrelated families reported, consistent feature is ID. PMID:25233840 reported a 6.5 year old female patient with a homozygous missense variant c.1273G > A (p.Gly425Arg) and her clinical presentation included intractable seizures, developmental delay, microcephaly, dysostosis, osteopenia, craniofacial dysmorphism, macrocytosis and megaloblastoid erythropoiesis. PMID:29784638 reported three siblings with homozygous variant c.289G>C (p.Gly97Arg) in RBSN. The proband presented global developmental delay, had complete 46,XY male-to-female sex reversal and died at age 20 months after multiple infections. The other 2 affected siblings underwent unrelated-donor bone marrow or stem cell transplantation at 8 and 6.5 months of age, respectively. Both have severe intellectual disability and are nonambulatory and nonverbal. PMID:35652444 reported two unrelated families (three siblings from a family of Iranian descent identified with homozygous variant c.547G>A (p.Gly183Arg) and four members from a family of indigenous Cree descent identified with homozygous variant c.538C>G (p.Arg180Gly)) with overlapping phenotypes including developmental delay, intellectual disability, distal motor axonal neuropathy and facial dysmorphism. Sources: Literature |
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| Mendeliome v1.644 | C1GALT1C1 | Ain Roesley Phenotypes for gene: C1GALT1C1 were changed from Tn polyagglutination syndrome, somatic MIM#300622 to Tn polyagglutination syndrome, somatic MIM#300622; atypical haemolytic-uremic syndrome MONDO#0016244, C1GALT1C1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.643 | C1GALT1C1 | Ain Roesley Publications for gene: C1GALT1C1 were set to 18537974; 16251947 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.642 | C1GALT1C1 |
Ain Roesley edited their review of gene: C1GALT1C1: Added comment: Red association for aHUS 1x male with de novo p.(Thr89Ile) which is absent in gnomAD v2 and v3 and has very high conservation; Changed publications: 18537974, 16251947, 36599939; Changed phenotypes: Tn polyagglutination syndrome, somatic MIM#300622, atypical haemolytic-uremic syndrome MONDO#0016244, C1GALT1C1-related |
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| Mendeliome v1.530 | MPC2 |
Zornitza Stark gene: MPC2 was added gene: MPC2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MPC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MPC2 were set to 36417180 Phenotypes for gene: MPC2 were set to mitochondrial pyruvate carrier deficiency, MONDO:0013877, MPC2-related Review for gene: MPC2 was set to AMBER Added comment: Four patients from two unrelated consanguineous families reported with homozygous variants (missense and stop-loss). Siblings from family 1 were diagnosed prenatally with diffuse subcutaneous oedema, cardiomegaly, corpus callosum agenesis, ventriculomegaly and hypoplasia of the cerebellum. Siblings from family 2 had slightly different presentations, which included anoxo-ischemic encephalopathy, isolated dyspnea, neonatal respiratory distress, neonatal jaundice, hypotonia, visual impairment, microcephaly; both siblings had severe delayed psychomotor development. Immunoblot analysis of protein expression in lysates from patient-derived fibroblasts demonstrated reduced MPC1 and MPC2 protein levels. Sources: Literature |
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| Mendeliome v1.511 | NPC1 |
Naomi Baker gene: NPC1 was added gene: NPC1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NPC1 were set to 36417180 Phenotypes for gene: NPC1 were set to mitochondrial pyruvate carrier deficiency, MONDO:0013877, MPC2-related Review for gene: NPC1 was set to AMBER Added comment: Four patients from two unrelated consanguineous families reported with homozygous variants (missense and stop-loss). Siblings from family 1 were diagnosed prenatally with diffuse subcutaneous oedema, cardiomegaly, corpus callosum agenesis, ventriculomegaly and hypoplasia of the cerebellum. Siblings from family 2 had slightly different presentations, which included anoxo-ischemic encephalopathy, isolated dyspnea, neonatal respiratory distress, neonatal jaundice, hypotonia, visual impairment, microcephaly; both siblings had severe delayed psychomotor development. Immunoblot analysis of protein expression in lysates from patient-derived fibroblasts demonstrated reduced MPC1 and MPC2 protein levels. Sources: Literature |
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| Mendeliome v1.491 | KIF26A |
Chirag Patel gene: KIF26A was added gene: KIF26A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KIF26A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF26A were set to PMID: 36228617 Phenotypes for gene: KIF26A were set to Congenital brain malformations, no OMIM # Review for gene: KIF26A was set to GREEN Added comment: 5 unrelated patients with biallelic loss-of-function variants in KIF26A (found through WES), exhibiting a spectrum of congenital brain malformations (schizencephaly, corpus callosum anomalies, polymicrgyria, and ventriculomegaly). Combining mice and human iPSC-derived organoid models, they discovered that loss of KIF26A causes excitatory neuron-specific defects in radial migration, localization, dendritic and axonal growth, and apoptosis, offering a convincing explanation of the disease etiology in patients. Single-cell RNA sequencing in KIF26A knockout organoids revealed transcriptional changes in MAPK, MYC, and E2F pathways. Sources: Literature |
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| Mendeliome v1.421 | CLCN7 |
Zornitza Stark changed review comment from: Two individuals reported with same missense variant and hypopigmentation, organomegaly, and delayed myelination and development. Variant is GoF. No osteopetrosis, biopsy findings from skin and other organs are consistent with a lysosomal storage disorder. IUGR, prematurity and polyhydramnios are features. Bi-allelic variants in this gene are associated with osteopetrosis.; to: Two individuals reported with same missense variant and hypopigmentation, organomegaly, and delayed myelination and development. Variant is GoF. No osteopetrosis, biopsy findings from skin and other organs are consistent with a lysosomal storage disorder. IUGR, prematurity and polyhydramnios are features. Mono- and bi-allelic variants in this gene are associated with osteopetrosis. |
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| Mendeliome v1.421 | CLCN7 | Zornitza Stark edited their review of gene: CLCN7: Changed phenotypes: Hypopigmentation, organomegaly, and delayed myelination and development, MIM# 618541, Osteopetrosis, autosomal dominant 2, MIM# 166600, Osteopetrosis, autosomal recessive 4, MIM# 611490 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.406 | GALNS | Zornitza Stark Tag treatable tag was added to gene: GALNS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.385 | VPS33A |
Bryony Thompson changed review comment from: PMID: 28013294 - 13 cases homozygous for VPS33A c.1492C>T p.(Arg498Trp) from non-consanguineous Yakuti families with a Mucopolysaccharidoses-like disease (coarse facial features, skeletal abnormalities, hepatosplenomegaly, respiratory problems, intellectual disability, and excess secretion of urinary glycosaminoglycans). Lysosomal over-acidification and heparan sulphate accumulation were detected in patient-derived and VPS33A-depleted HeLa cells. PMID: 27547915 - 2 affected siblings homozygous for VPS33A p.(Arg498Trp) from a consanguineous Turkish family PMID: 31936524 - 1 homozygous case from a non-consanguineous Yakuti family PMID: 36153662 - an attenuated juvenile case with a new homozygous missense variant VPS33A c.599G>C p.(Arg200Pro). Urinary glycosaminoglycan analysis revealed increased heparan, dermatan sulphates, and hyaluronic acid and decreased abundance of VPS33A in patient-derived fibroblasts; to: Now two missense variants reported with disease in at least 15 probands/families PMID: 28013294 - 13 cases homozygous for VPS33A c.1492C>T p.(Arg498Trp) from non-consanguineous Yakuti families with a Mucopolysaccharidoses-like disease (coarse facial features, skeletal abnormalities, hepatosplenomegaly, respiratory problems, intellectual disability, and excess secretion of urinary glycosaminoglycans). Lysosomal over-acidification and heparan sulphate accumulation were detected in patient-derived and VPS33A-depleted HeLa cells. PMID: 27547915 - 2 affected siblings homozygous for VPS33A p.(Arg498Trp) from a consanguineous Turkish family PMID: 31936524 - 1 homozygous case from a non-consanguineous Yakuti family PMID: 36153662 - an attenuated juvenile case with a new homozygous missense variant VPS33A c.599G>C p.(Arg200Pro). Urinary glycosaminoglycan analysis revealed increased heparan, dermatan sulphates, and hyaluronic acid and decreased abundance of VPS33A in patient-derived fibroblasts |
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| Mendeliome v1.381 | GALT | Zornitza Stark reviewed gene: GALT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Galactosemia MIM#230400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.381 | GALT | Zornitza Stark Mode of inheritance for gene: GALT was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.348 | NSD2 | Zornitza Stark edited their review of gene: NSD2: Added comment: PMID 36189577: two individuals reported with a GoF variant, p.Glu1099Lys, and a distinct phenotype: intellectual disability, coarse/ square facial gestalt, abnormalities of the hands, and organomegaly.; Changed phenotypes: Rauch-Steindl syndrome, MIM# 619695, Microcephaly, intellectual disability, Neurodevelopmental disorder, NSD2-associated, GoF, MONDO:0700092 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.346 | TRAF3 | Zornitza Stark edited their review of gene: TRAF3: Added comment: PMID 35960817: Nine individuals from five unrelated families with childhood-onset immune diseases and recurrent infections. All patients had suffered recurrent ear and sinopulmonary infections, including pneumonias from encapsulated bacteria Streptococcus pneumoniae and Haemophilus influenza, resulting in early-onset bronchiectasis in several individuals; Changed rating: GREEN; Changed publications: 20832341, 35960817; Changed phenotypes: Autoinflammatory syndrome, TRAF3-related, MONDO:0019751, hypergammaglobulinemia, lymphadenopathy, splenomegaly, Sjögren’s syndrome, {?Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 5}, MIM# 614849 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.343 | GALE | Zornitza Stark Tag treatable tag was added to gene: GALE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.343 | GALK1 | Zornitza Stark Tag treatable tag was added to gene: GALK1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.343 | GALT | Zornitza Stark Tag treatable tag was added to gene: GALT. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.35 | GIMAP6 |
Elena Savva gene: GIMAP6 was added gene: GIMAP6 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GIMAP6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GIMAP6 were set to PMID: 35551368; 33328581 Phenotypes for gene: GIMAP6 were set to Autophagy, immune competence and inflammation Review for gene: GIMAP6 was set to AMBER Added comment: PMID: 35551368, PMID: 33328581 - K/O mice show autophagy, redox regulation, and polyunsaturated fatty acid (PUFA)–containing lipids and die prematurely from microangiopathic glomerulosclerosis with immunodeficiency. - 2 unrelated families (3 patients) w/ a homozygous missense (p.Gly153Val) and nonsense (p.Trp86*). All unaffected siblings were heterozygous. Patient 1 (missense) presented with Coombs-positive hemolytic anemia, hepatosplenomegaly, Cranial MRI showed bilateral effusions, sulcal hyperintensity, and lateral parietal subcortical acute focal ischemic lesions. Patient 2 (nonsense) presented with recurrent purulent otitis media and a chronic wet cough, persistent jaundice, recurrent chest and ear infections, lingular consolidation, mild bronchiectasis, bibasilar bronchial wall thickening, right peribronchial consolidation, right lower lobe bronchiectasis, bilateral axillary lymphadenopathy, and splenomegaly. Patient 3 (nonsense) presented with suffered headaches, abdomen pain, mouth ulcers, and recurrent infections - Functional studies show patient 1 (missense) with reduced protein expression on western blot, and patient 2/3 (nonsense) with no protein expression. T cells of Pt 1 were similar to mouse K/O model (elevated basal LC3-II, reduced autophagic flux). gnomAD: 0 homozygous PTCs, but a very common canonical splice which is present in the non-canonical transcript Sources: Literature |
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| Mendeliome v1.15 | IKBKG |
Zornitza Stark edited their review of gene: IKBKG: Added comment: X-linked systemic autoinflammatory disease (SAIDX) is characterized by the onset of systemic autoinflammation in the first months of life. Features include lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional manifestations may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy. Laboratory studies show hypogammaglobulinemia, increased or decreased white blood cell count, autoimmune cytopenias, elevated serum inflammatory markers, and a type I interferon signature. 6 unrelated boys and a girl reported. All variants resulted in absence of the domain encoded by exon 5 (NEMOdelEx5). Note variants in this gene are associated with immunodeficiency +/- ectodermal features and with IP.; Changed phenotypes: Ectodermal dysplasia and immunodeficiency 1, MIM# 300291, Immunodeficiency 33 , MIM#300636, Incontinentia pigmenti, MIM# 308300, Autoinflammatory disease, systemic, X-linked, MIM# 301081 |
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| Mendeliome v0.14755 | ADD1 | Zornitza Stark Phenotypes for gene: ADD1 were changed from Intellectual disability, corpus callosum dysgenesis, and ventriculomegaly; no OMIM # to Neurodevelopmental disorder MONDO:0700092, ADD1-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14726 | GALNT2 | Zornitza Stark Marked gene: GALNT2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14726 | GALNT2 | Zornitza Stark Gene: galnt2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14726 | GALNT2 | Zornitza Stark Phenotypes for gene: GALNT2 were changed from Congenital disorder of glycosylation to Congenital disorder of glycosylation MONDO:0015286 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14725 | GALNT3 | Zornitza Stark Marked gene: GALNT3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14725 | GALNT3 | Zornitza Stark Gene: galnt3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14725 | GALNT3 | Zornitza Stark Phenotypes for gene: GALNT3 were changed from to Tumoral calcinosis, hyperphosphatemic, familial, 1, MIM# 211900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14724 | GALNT3 | Zornitza Stark Publications for gene: GALNT3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14723 | GALNT3 | Zornitza Stark Mode of inheritance for gene: GALNT3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14722 | GALT | Zornitza Stark Marked gene: GALT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14722 | GALT | Zornitza Stark Gene: galt has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14722 | GALT | Zornitza Stark Phenotypes for gene: GALT were changed from to Galactosaemia MIM#230400; Disorders of galactose metabolism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14721 | GALT | Zornitza Stark Publications for gene: GALT were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14720 | GALT | Zornitza Stark Mode of inheritance for gene: GALT was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14650 | ADD1 |
Chirag Patel gene: ADD1 was added gene: ADD1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ADD1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: ADD1 were set to PMID: 34906466 Phenotypes for gene: ADD1 were set to Intellectual disability, corpus callosum dysgenesis, and ventriculomegaly; no OMIM # Review for gene: ADD1 was set to GREEN Added comment: 4 unrelated individuals affected by ID and/or complete or partial agenesis of corpus callosum, and enlarged lateral ventricles. WES found loss-of-function variants - 1 recessive missense variant and 3 de novo variants. The recessive variant is associated with ACC and enlarged lateral ventricles, and the de novo variants were associated with complete or partial agenesis of corpus callosum, mild ID and attention deficit. Human variants impair ADD1 protein expression and/or dimerization with ADD2. Add1 knockout mice recapitulate corpus callosum dysgenesis and ventriculomegaly phenotypes. Three adducin genes (ADD1, ADD2, and ADD3) encode cytoskeleton proteins that are critical for osmotic rigidity and cell shape. ADD1, ADD2, and ADD3 form heterodimers (ADD1/ADD2, ADD1/ADD3), which further form heterotetramers. Adducins interconnect spectrin and actin filaments to form polygonal scaffolds beneath the cell membranes and form ring-like structures in neuronal axons. Adducins regulate mouse neural development, but their function in the human brain is unknown Sources: Literature |
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| Mendeliome v0.14579 | GALNT3 | Chirag Patel reviewed gene: GALNT3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15133511, 20358599, 32125652; Phenotypes: Tumoral calcinosis, hyperphosphatemic, familial, 1, MIM# 211900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14309 | MTHFD1 | Zornitza Stark Publications for gene: MTHFD1 were set to Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinaemia MIM # 617780 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14308 | MTHFD1 | Zornitza Stark Phenotypes for gene: MTHFD1 were changed from to Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinaemia MIM # 617780 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14260 | WDR4 | Zornitza Stark Phenotypes for gene: WDR4 were changed from to Galloway-Mowat syndrome 6, OMIM #618347; Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.14257 | WDR4 | Zornitza Stark reviewed gene: WDR4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26416026, 30079490, 29597095, 28617965; Phenotypes: Galloway-Mowat syndrome 6, OMIM #618347, Microcephaly, growth deficiency, seizures, and brain malformations, OMIM #618346; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13596 | HEPACAM | Zornitza Stark Phenotypes for gene: HEPACAM were changed from to Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM# 613925; Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, MIM# 613926 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13593 | HEPACAM | Zornitza Stark reviewed gene: HEPACAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 21419380, 21419380; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM# 613925, Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, MIM# 613926; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13592 | DNASE2 | Zornitza Stark Phenotypes for gene: DNASE2 were changed from Auto-inflammatory disorder; splenomegaly; glomerulonephritis; liver fibrosis; arthritis; HLH to Autoinflammatory-pancytopaenia syndrome, MIM# 619858 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13481 | B4GALT1 | Zornitza Stark Marked gene: B4GALT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13481 | B4GALT1 | Zornitza Stark Gene: b4galt1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13481 | B4GALT1 | Zornitza Stark Phenotypes for gene: B4GALT1 were changed from to Congenital disorder of glycosylation, type Iid, MIM#607091 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13480 | B4GALT1 | Zornitza Stark Publications for gene: B4GALT1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13479 | B4GALT1 | Zornitza Stark Mode of inheritance for gene: B4GALT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13478 | B4GALNT1 | Zornitza Stark Marked gene: B4GALNT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13478 | B4GALNT1 | Zornitza Stark Gene: b4galnt1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13478 | B4GALNT1 | Zornitza Stark Phenotypes for gene: B4GALNT1 were changed from to Spastic paraplegia 26, autosomal recessive (MIM #609195) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13477 | B4GALNT1 | Zornitza Stark Publications for gene: B4GALNT1 were set to 23746551 24103911 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13476 | B4GALNT1 | Zornitza Stark Publications for gene: B4GALNT1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13475 | B4GALNT1 | Zornitza Stark Mode of inheritance for gene: B4GALNT1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13474 | B4GALNT1 | Zornitza Stark reviewed gene: B4GALNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23746551 24103911; Phenotypes: Spastic paraplegia 26, autosomal recessive (MIM #609195); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13398 | PIK3CA | Zornitza Stark Phenotypes for gene: PIK3CA were changed from to Megalencephaly-capillary malformation (MCAP) syndrome , MIM#602501; CLAPO syndrome, somatic, MIM# 613089; CLOVE syndrome, somatic, MIM# 612918 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13396 | PIK3CA | Zornitza Stark reviewed gene: PIK3CA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-capillary malformation (MCAP) syndrome , MIM#602501, CLAPO syndrome, somatic, MIM# 613089, CLOVE syndrome, somatic, MIM# 612918; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13367 | PIK3R2 | Zornitza Stark Phenotypes for gene: PIK3R2 were changed from to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, MIM# 603387 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13364 | PIK3R2 | Zornitza Stark reviewed gene: PIK3R2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22729224, 23745724, 33604570; Phenotypes: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, MIM# 603387; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12667 | SLC2A2 |
Zornitza Stark changed review comment from: Fanconi-Bickel syndrome is a rare but well-defined clinical entity, inherited in an autosomal recessive mode and characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose. > 5 patients previously reported with the associated condition, which is a glycogen storage disease. SLC2A2 encodes for the glucose transporter, GLUT2.; to: Fanconi-Bickel syndrome is characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose. > 5 patients previously reported with the associated condition, which is a glycogen storage disease. SLC2A2 encodes for the glucose transporter, GLUT2. |
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| Mendeliome v0.12316 | AKT3 | Elena Savva Phenotypes for gene: AKT3 were changed from to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 MIM#615937 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12314 | AKT3 | Elena Savva reviewed gene: AKT3: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 22729224; Phenotypes: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 MIM#615937; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11395 | C1GALT1C1 | Zornitza Stark Publications for gene: C1GALT1C1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11362 | C1GALT1C1 | Ain Roesley Marked gene: C1GALT1C1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11362 | C1GALT1C1 | Ain Roesley Gene: c1galt1c1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11362 | C1GALT1C1 | Ain Roesley Phenotypes for gene: C1GALT1C1 were changed from to Tn polyagglutination syndrome, somatic MIM#300622 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11361 | C1GALT1C1 | Ain Roesley Mode of inheritance for gene: C1GALT1C1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11360 | C1GALT1C1 | Ain Roesley reviewed gene: C1GALT1C1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18537974, 16251947; Phenotypes: Tn polyagglutination syndrome, somatic MIM#300622; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11044 | RNASET2 | Zornitza Stark Phenotypes for gene: RNASET2 were changed from to Leukoencephalopathy, cystic, without megalencephaly MIM#612951 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11016 | B3GALNT1 | Zornitza Stark Marked gene: B3GALNT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11016 | B3GALNT1 | Zornitza Stark Gene: b3galnt1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11016 | B3GALNT1 | Zornitza Stark Phenotypes for gene: B3GALNT1 were changed from to Blood group, globoside system MIM#615021 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11015 | B3GALNT1 | Zornitza Stark Classified gene: B3GALNT1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11015 | B3GALNT1 | Zornitza Stark Gene: b3galnt1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11011 | RNASET2 | Ain Roesley reviewed gene: RNASET2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31349848, 19525954, 27091087, 29336640, 18545798, 15851732; Phenotypes: Leukoencephalopathy, cystic, without megalencephaly MIM#612951; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11004 | B3GALNT1 | Paul De Fazio reviewed gene: B3GALNT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Blood group, globoside system MIM#615021; Mode of inheritance: Unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10917 | ABCB4 | Zornitza Stark Phenotypes for gene: ABCB4 were changed from Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism to Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism; Gallbladder disease 1 (MIM#600803) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10913 | ABCB4 | Lucy Spencer reviewed gene: ABCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18482588, 28924228, 32376413; Phenotypes: Cholestasis, intrahepatic, of pregnancy, 3 (MIM#614972), Gallbladder disease 1 (MIM#600803); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10656 | STRADA | Zornitza Stark Phenotypes for gene: STRADA were changed from to Polyhydramnios, megalencephaly, and symptomatic epilepsy, OMIM:611087; Polyhydramnios, megalencephaly, and symptomatic epilepsy, MONDO:0012611 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10653 | STRADA | Zornitza Stark reviewed gene: STRADA: Rating: GREEN; Mode of pathogenicity: None; Publications: 17522105, 27170158, 28688840; Phenotypes: Polyhydramnios, megalencephaly, and symptomatic epilepsy, OMIM:611087, Polyhydramnios, megalencephaly, and symptomatic epilepsy, MONDO:0012611; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10649 | WDR73 | Zornitza Stark Phenotypes for gene: WDR73 were changed from to Galloway-Mowat syndrome 1, MIM#251300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10646 | WDR73 | Zornitza Stark reviewed gene: WDR73: Rating: GREEN; Mode of pathogenicity: None; Publications: 25466283, 26123727, 25873735, 26070982, 30315938; Phenotypes: Galloway-Mowat syndrome 1 MIM#251300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10561 | CCND2 | Alison Yeung Phenotypes for gene: CCND2 were changed from to Neurodevelopmental disorder, CCND2-related MONDO: 0700092; Microcephaly, MONDO: 0001149; Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3, MIM# 615938 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10250 | REL |
Zornitza Stark changed review comment from: Second unrelated individual reported, homozygous splice site variant. Immunodeficiency-92 (IMD92) is an autosomal recessive primary immunodeficiency characterized by the onset of recurrent infections in infancy or early childhood. Infectious agents are broad, including bacterial, viral, fungal, and parasitic, including Cryptosporidium and Mycobacteria. Patient lymphocytes show defects in both T- and B-cell proliferation, cytokine secretion, and overall function, and there is also evidence of dysfunction of NK, certain antigen-presenting cells, and myeloid subsets.; to: Second unrelated individual reported, with a different homozygous splice site variant. Immunodeficiency-92 (IMD92) is an autosomal recessive primary immunodeficiency characterized by the onset of recurrent infections in infancy or early childhood. Infectious agents are broad, including bacterial, viral, fungal, and parasitic, including Cryptosporidium and Mycobacteria. Patient lymphocytes show defects in both T- and B-cell proliferation, cytokine secretion, and overall function, and there is also evidence of dysfunction of NK, certain antigen-presenting cells, and myeloid subsets. |
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| Mendeliome v0.10250 | REL |
Zornitza Stark edited their review of gene: REL: Added comment: Second unrelated individual reported, homozygous splice site variant. Immunodeficiency-92 (IMD92) is an autosomal recessive primary immunodeficiency characterized by the onset of recurrent infections in infancy or early childhood. Infectious agents are broad, including bacterial, viral, fungal, and parasitic, including Cryptosporidium and Mycobacteria. Patient lymphocytes show defects in both T- and B-cell proliferation, cytokine secretion, and overall function, and there is also evidence of dysfunction of NK, certain antigen-presenting cells, and myeloid subsets.; Changed rating: AMBER; Changed publications: 31103457, 34623332; Changed phenotypes: Immunodeficiency 92, MIM# 619652, Combined immunodeficiency, T cells: normal, decreased memory CD4, poor proliferation, B cells: low, mostly naive, few switched memory B cells, impaired proliferation, Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic organisms, Defective innate immunity |
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| Mendeliome v0.10224 | GALE | Zornitza Stark Marked gene: GALE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10224 | GALE | Zornitza Stark Gene: gale has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10224 | GALK1 | Zornitza Stark Marked gene: GALK1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10224 | GALK1 | Zornitza Stark Gene: galk1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10224 | GALE | Zornitza Stark Phenotypes for gene: GALE were changed from to Galactose epimerase deficiency MIM#230350; Disorders of galactose metabolism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10223 | GALE | Zornitza Stark Publications for gene: GALE were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10216 | GALE | Zornitza Stark Mode of inheritance for gene: GALE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10215 | GALK1 | Zornitza Stark Phenotypes for gene: GALK1 were changed from to Galactokinase deficiency with cataracts MIM#230200; Disorders of galactose metabolism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10214 | GALK1 | Zornitza Stark Publications for gene: GALK1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10213 | GALK1 | Zornitza Stark Mode of inheritance for gene: GALK1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10071 | CLCN7 | Zornitza Stark Phenotypes for gene: CLCN7 were changed from to Hypopigmentation, organomegaly, and delayed myelination and development, MIM# 618541; Osteopetrosis, autosomal recessive 4, MIM# 611490 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10068 | CLCN7 | Zornitza Stark reviewed gene: CLCN7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31155284; Phenotypes: Hypopigmentation, organomegaly, and delayed myelination and development, MIM# 618541, Osteopetrosis, autosomal recessive 4, MIM# 611490; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10054 | MMP15 |
Zornitza Stark gene: MMP15 was added gene: MMP15 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: MMP15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MMP15 were set to 33875846 Phenotypes for gene: MMP15 were set to Cholestasis; Congenital heart disease Review for gene: MMP15 was set to AMBER Added comment: Three individuals from two families with bi-allelic variants and very similar phenotype including rare combination of symtoms (Alagille-like) cholestasis with hepatomegaly and congenital heart disease. Sources: Literature |
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| Mendeliome v0.9823 | MLC1 | Zornitza Stark Phenotypes for gene: MLC1 were changed from to Megalencephalic leukoencephalopathy with subcortical cysts (MIM#604004) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9779 | MLC1 | Daniel Flanagan reviewed gene: MLC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11254442, 18757878, 16652334; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts (MIM#604004); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9698 | GON7 | Zornitza Stark Phenotypes for gene: GON7 were changed from Galloway-Mowat syndrome to Galloway-Mowat syndrome 9, MIM# 619603 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9697 | GON7 | Zornitza Stark edited their review of gene: GON7: Changed phenotypes: Galloway-Mowat syndrome 9, MIM# 619603 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9510 | FAN1 | Zornitza Stark Phenotypes for gene: FAN1 were changed from to Interstitial nephritis, karyomegalic, MIM# 614817 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9507 | FAN1 | Zornitza Stark reviewed gene: FAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22772369, 16678356, 7847351, 8546134; Phenotypes: Interstitial nephritis, karyomegalic, MIM# 614817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9338 | AIP |
Paul De Fazio changed review comment from: Germline variants in AIP cause predisposition to pituitary adenomas which may result in acromegaly. A 2015 cohort study of 143 patients with pituitary gigantism who consented to genetic testing found 29% had variants in AIP. Age at first symptoms was 9-13 years, age at diagnosis 14-20 years.; to: Germline variants in AIP cause predisposition to pituitary adenomas which may result in acromegaly. A 2015 cohort study of 143 patients with pituitary gigantism who consented to genetic testing found 29% had variants in AIP. Age at first symptoms was 9-13 years, age at diagnosis 14-20 years. Many patients have no family history, suggesting low penetrance. |
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| Mendeliome v0.9297 | ATP11A |
Elena Savva gene: ATP11A was added gene: ATP11A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ATP11A were set to PMID: 34403372 Phenotypes for gene: ATP11A were set to Neurological disorder Mode of pathogenicity for gene: ATP11A was set to Other Review for gene: ATP11A was set to AMBER Added comment: PMID: 34403372: - Single de novo missense variant reported in a patient with developmental delay and neurological deterioration. - Patient MRI showed severe cerebral atrophy, ventriculomegaly, hypomyelination leukodystrophy, thinned corpus callosum. Axonal neuropathy suggested. - K/I heterozygous mice died perinatally. - Functional studies on missense variant show plasma membrane lipid content impairment, reduced ATPase activity etc. gnomAD: some NMD PTCs present, good quality variants found with 4-5 hets. Sources: Literature |
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| Mendeliome v0.9137 | MTRR | Zornitza Stark Phenotypes for gene: MTRR were changed from to Homocystinuria-megaloblastic anaemia, cbl E type, MIM# 236270 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9134 | MTRR | Zornitza Stark reviewed gene: MTRR: Rating: GREEN; Mode of pathogenicity: None; Publications: 12555939, 15714522; Phenotypes: Homocystinuria-megaloblastic anaemia, cbl E type, MIM# 236270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9134 | MTR | Zornitza Stark Phenotypes for gene: MTR were changed from to Homocystinuria-megaloblastic anaemia, cblG complementation type, MIM# 250940 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9131 | MTR | Zornitza Stark reviewed gene: MTR: Rating: GREEN; Mode of pathogenicity: None; Publications: 8968736, 8968737, 9683607, 12068375; Phenotypes: Homocystinuria-megaloblastic anaemia, cblG complementation type, MIM# 250940; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9101 | UMPS |
Zornitza Stark edited their review of gene: UMPS: Added comment: 20 unrelated patients have been reported with biallelic missense variants; one mouse model Orotic aciduria is characterised by megaloblastic anaemia and orotic acid crystalluria, frequently associated with a degree of physical and intellectual disability. Other features include, congenital malformations (Atrial/ Ventricular septal defect) and immunodeficiencies (T-cell dysfunction, failure to thrive, recurrent infections). Haematology features - Megaloblastic anaemia - Low to normal reticulocyte count - Anisocytosis - Poikilocytosis - Hypochromia; Changed publications: 9042911, 33489760; Changed phenotypes: Orotic aciduria, MIM# 258900 |
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| Mendeliome v0.9098 | YARS2 | Zornitza Stark Phenotypes for gene: YARS2 were changed from to Myopathy, lactic acidosis, and sideroblastic anaemia 2 MIM# 613561; sideroblastic anaemia; muscle atrophy; myopathy; lactic acidosis; Hypertrophic cardiomyopathy; Hepatomegaly; Decreased cytochrome C oxidase activity | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9095 | YARS2 | Zornitza Stark reviewed gene: YARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24430573, 24344687; Phenotypes: Myopathy, lactic acidosis, and sideroblastic anaemia 2 MIM# 613561, sideroblastic anaemia, muscle atrophy, myopathy, lactic acidosis, Hypertrophic cardiomyopathy, Hepatomegaly, Decreased cytochrome C oxidase activity; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9054 | DHFR | Zornitza Stark Phenotypes for gene: DHFR were changed from to Megaloblastic anaemia due to dihydrofolate reductase deficiency, MIM# 613839 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9051 | DHFR | Zornitza Stark reviewed gene: DHFR: Rating: GREEN; Mode of pathogenicity: None; Publications: 21310276, 21310277; Phenotypes: Megaloblastic anaemia due to dihydrofolate reductase deficiency, MIM# 613839; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9023 | KIDINS220 | Zornitza Stark Phenotypes for gene: KIDINS220 were changed from Spastic paraplegia, intellectual disability, nystagmus, and obesity, MIM# 617296; cerebral ventriculomegaly; limb contractures to Spastic paraplegia, intellectual disability, nystagmus, and obesity, MIM# 617296; Ventriculomegaly and arthrogryposis, MIM# 619501 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9022 | KIDINS220 | Zornitza Stark edited their review of gene: KIDINS220: Changed phenotypes: Spastic paraplegia, intellectual disability, nystagmus, and obesity, MIM# 617296, Ventriculomegaly and arthrogryposis, MIM# 619501 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8984 | PNPLA6 |
Zornitza Stark changed review comment from: Ataxia is part of the phenotype. Sources: Expert list; to: Variants in this gene are associated with multiple phenotypes. Oliver-McFarlane syndrome is a rare congenital disorder characterized by trichomegaly, severe chorioretinal atrophy and multiple pituitary hormone deficiencies, including growth hormone. At least 10 families reported. Laurence-Moon syndrome has a clinical presentation similar to that of Oliver-McFarlane syndrome, including chorioretinopathy and pituitary dysfunction, but with childhood onset of ataxia, peripheral neuropathy, and spastic paraplegia and without trichomegaly. Single family reported. |
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| Mendeliome v0.8946 | RAG1 | Zornitza Stark Phenotypes for gene: RAG1 were changed from to Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889; Combined cellular and humoral immune defects with granulomas MIM# 233650; Omenn syndrome MIM# 603554; Severe combined immunodeficiency, B cell-negative MIM# 601457 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8937 | RAG1 | Danielle Ariti reviewed gene: RAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16276422, 18463379, 20489056, 9630231, 11313270, 17476359, 8810255, 6823332; Phenotypes: Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889, Combined cellular and humoral immune defects with granulomas MIM# 233650, Omenn syndrome MIM# 603554, Severe combined immunodeficiency, B cell-negative MIM# 601457; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8935 | MTHFD1 | Danielle Ariti reviewed gene: MTHFD1: Rating: GREEN; Mode of pathogenicity: None; Publications: Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinaemia MIM # 617780, Decreased Ig levels, poor antibody responses to conjugated polysaccharide antigens, low B/T/NK cells, Recurrent bacterial infection, megaloblastic anaemia, failure to thrive, neutropenia, seizures, intellectual disability, folate-responsive, Lymphopaenia; Phenotypes: 32414565, 19033438; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8776 | STK4 | Zornitza Stark Phenotypes for gene: STK4 were changed from to T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations MIM# 614868; CD4/CD8 lymphopaenia; cardiac malformations; reduced naïve T cells; increased TEM and TEMRA cells; poor T cell Proliferation; Reduced memory B cells; Reduced IgM, increased IgG, IgA, IgE; impaired antibody responses; intermittent neutropaenia; bacterial/ viral/ fungal infections; autoimmune cytopaenias; mucocutaneous candidiasis; cutaneous warts | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8773 | SP110 | Zornitza Stark Phenotypes for gene: SP110 were changed from to Hepatic veno-occlusive disease with immunodeficiency MIM#235550; Hepatic veno-occlusive disease; susceptibility to Pneumocystis jirovecii pneumonia; cytomegalovirus; thrombocytopaenia; hepatosplenomegaly; cerebrospinal leukodystrophy; memory T/B cell deficiency; low Ig levels; absent tissue plasma cells; absent lymph node germinal centers; hypogammaglobulinaemia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8770 | SMARCAL1 | Zornitza Stark Phenotypes for gene: SMARCAL1 were changed from to Schimke immune-osseous dysplasia MIM# 242900; T cell deficiency; Short stature; spondyloepiphyseal dysplasia; renal dysfunction; lymphocytopaenia; nephropathy; bacterial/viral/fungal infections; may present as SCID; bone marrow failure | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8767 | STK4 | Danielle Ariti reviewed gene: STK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22294732, 26117625, 22174160, 22952854; Phenotypes: T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations MIM# 614868, CD4/CD8 lymphopaenia, cardiac malformations, reduced naïve T cells, increased TEM and TEMRA cells, poor T cell Proliferation, Reduced memory B cells, Reduced IgM, increased IgG, IgA, IgE, impaired antibody responses, intermittent neutropaenia, bacterial/ viral/ fungal infections, autoimmune cytopaenias, mucocutaneous candidiasis, cutaneous warts; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8767 | SP110 | Danielle Ariti reviewed gene: SP110: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301448, 31721003; Phenotypes: Hepatic veno-occlusive disease with immunodeficiency MIM#235550, Hepatic veno-occlusive disease, susceptibility to Pneumocystis jirovecii pneumonia, cytomegalovirus, thrombocytopaenia, hepatosplenomegaly, cerebrospinal leukodystrophy, memory T/B cell deficiency, low Ig levels, absent tissue plasma cells, absent lymph node germinal centers, hypogammaglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8767 | SMARCAL1 | Danielle Ariti reviewed gene: SMARCAL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301550, 17089404, 20036229; Phenotypes: Schimke immune-osseous dysplasia MIM# 242900, T cell deficiency, Short stature, spondyloepiphyseal dysplasia, renal dysfunction, lymphocytopaenia, nephropathy, bacterial/viral/fungal infections, may present as SCID, bone marrow failure; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8735 | COLGALT1 | Bryony Thompson Marked gene: COLGALT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8735 | COLGALT1 | Bryony Thompson Gene: colgalt1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8735 | COLGALT1 | Bryony Thompson Classified gene: COLGALT1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8735 | COLGALT1 | Bryony Thompson Gene: colgalt1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8734 | COLGALT1 |
Bryony Thompson gene: COLGALT1 was added gene: COLGALT1 was added to Mendeliome. Sources: Other Mode of inheritance for gene: COLGALT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COLGALT1 were set to 30412317; 33709034; 31759980 Phenotypes for gene: COLGALT1 were set to Brain small vessel disease 3 MIM#618360 Review for gene: COLGALT1 was set to GREEN Added comment: 3 unrelated cases with biallelic variants, and supporting functional assays. The main features of the cases were porencephalic cysts, leukoencephalopathy, lacunar infarcts, cerebral microbleeds/haemorrhages and calcifications. A null mouse model was embryonic lethal, but had defects in the vascular networks of the embryos. Sources: Other |
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| Mendeliome v0.8632 | GIMAP5 |
Zornitza Stark gene: GIMAP5 was added gene: GIMAP5 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: GIMAP5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GIMAP5 were set to 33956074 Phenotypes for gene: GIMAP5 were set to Portal hypertension, noncirrhotic, 2, MIM# 619463 Review for gene: GIMAP5 was set to GREEN Added comment: 8 individuals from 4 unrelated families reported with onset of disease in the first decade of life. Clinical features included jaundice, hyperbilirubinaemia, pancytopaenia, including neutropaenia, lymphopaenia, and thrombocytopaenia, hepatosplenomegaly, and oesophageal varices. Some individuals had recurrent infections or features suggestive of an immunodeficiency. Liver biopsy was notable for the absence of cirrhosis and the presence of nodular regeneration. Sources: Expert list |
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| Mendeliome v0.8626 | MALT1 | Zornitza Stark Phenotypes for gene: MALT1 were changed from to Immunodeficiency 12 MIM# 615468; poor T-cell proliferation; normal T/B cell numbers; poor specific antibody response; recurrent bacterial/fungal/viral infections; bronchiectasis; failure to thrive | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8623 | IL2RG | Zornitza Stark Phenotypes for gene: IL2RG were changed from to Combined immunodeficiency, X-linked, moderate MIM# 312863; Severe combined immunodeficiency, X-linked MIM# 300400; recurrent viral/fungal/bacterial infections; Low T/NK cells; Low Ig levels; lymphocytopaenia; hypogammaglobulinaemia; failure to thrive; diarrhoea; Pneumonia; Thymic hypoplasia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8620 | IL2RG | Zornitza Stark reviewed gene: IL2RG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301584, 8462096, 8401490, 7883965, 9399950; Phenotypes: Combined immunodeficiency, X-linked, moderate MIM# 312863, Severe combined immunodeficiency, X-linked MIM# 300400, recurrent viral/fungal/bacterial infections, Low T/NK cells, Low Ig levels, lymphocytopaenia, hypogammaglobulinaemia, failure to thrive, diarrhoea, Pneumonia, Thymic hypoplasia; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8617 | ITK | Zornitza Stark Phenotypes for gene: ITK were changed from to Lymphoproliferative syndrome 1 MIM# 613011; Lymphadenopathy; Recurrent infections; Hypogammaglobulinaemia; Evidence of EBV infection; EBV associated B cell Lymphoproliferation; High EBV viral load; Normal-low serum Ig; Depleted CD4+ T cells; Anaemia; Thrombocytopaenia; Hepatosplenomegaly | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8614 | MALT1 |
Danielle Ariti edited their review of gene: MALT1: Added comment: 5 individuals from 3 unrelated families with immunodeficiency phenotype have reported variants in MALT1; two MALT1-knockout mouse models displaying primary T- and B-cell lymphocyte deficiency. Variants identified were homozygous missense variants resulting in the alteration of highly conserved residue domains. All individuals reported onset in infancy of recurrent bacterial/ fungal/ viral infections leading to bronchiectasis and poor T-cell proliferation.; Changed rating: GREEN |
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| Mendeliome v0.8614 | ITK | Danielle Ariti reviewed gene: ITK: Rating: GREEN; Mode of pathogenicity: None; Publications: 19425169, 22289921, 25061172, 26056787, 9311799, 10213685; Phenotypes: Lymphoproliferative syndrome 1 MIM# 613011, Lymphadenopathy, Recurrent infections, Hypogammaglobulinaemia, Evidence of EBV infection, EBV associated B cell Lymphoproliferation, High EBV viral load, Normal-low serum Ig, Depleted CD4+ T cells, Anaemia, Thrombocytopaenia, Hepatosplenomegaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8614 | MALT1 | Danielle Ariti reviewed gene: MALT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23727036, 24332264, 14576442, 31037583; Phenotypes: Immunodeficiency 12 MIM# 615468, poor T-cell proliferation, normal T/B cell numbers, poor specific antibody response, recurrent bacterial/fungal/viral infections, bronchiectasis, failure to thrive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8533 | DOCK8 | Zornitza Stark Phenotypes for gene: DOCK8 were changed from to Hyper-IgE recurrent infection syndrome, autosomal recessive MIM# 243700; T cell Lymphopaenia; decraese T/B/NK cells; Eosinophilia; low IgM; elevated IgE; recurrent cutaneous/ viral/ bacterial/ fungal/ infections; severe atopy/allergic disease; autoimmune haemolytic anaemia; eczema; cancer diathesis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8527 | DOCK8 | Danielle Ariti reviewed gene: DOCK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 19776401, 20622910, 21931011, 26659092, 19898472, 25422492; Phenotypes: Hyper-IgE recurrent infection syndrome, autosomal recessive MIM# 243700, T cell Lymphopaenia, decraese T/B/NK cells, Eosinophilia, low IgM, elevated IgE, recurrent cutaneous/ viral/ bacterial/ fungal/ infections, severe atopy/allergic disease, autoimmune haemolytic anaemia, eczema, cancer diathesisc; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8457 | CD27 | Zornitza Stark Phenotypes for gene: CD27 were changed from to Lymphoproliferative syndrome 2; CD27-deficiency MIM# 615122; hepatosplenomegaly; reduced CD8+ T-cell function; lymphadenopathy; hepatosplenomegaly; fever; increased susceptibility to EBV infection; aplastic anaemia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8454 | CD27 | Zornitza Stark reviewed gene: CD27: Rating: GREEN; Mode of pathogenicity: None; Publications: 22197273, 22801960, 22365582, 25843314, 11062504; Phenotypes: Lymphoproliferative syndrome 2, CD27-deficiency MIM# 615122, hepatosplenomegaly, reduced CD8+ T-cell function, lymphadenopathy, hepatosplenomegaly, fever, increased susceptibility to EBV infection, aplastic anaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8364 | CRB2 | Zornitza Stark Phenotypes for gene: CRB2 were changed from to Ventriculomegaly with cystic kidney disease, MIM# 219730; Focal segmental glomerulosclerosis 9, MIM# 616220 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8361 | CRB2 | Zornitza Stark edited their review of gene: CRB2: Changed publications: 25557780, 33687977, 32051522, 30212996, 33575434, 31438467, 30593785, 25557779; Changed phenotypes: Ventriculomegaly with cystic kidney disease, MIM# 219730, Focal segmental glomerulosclerosis 9, MIM# 616220 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7217 | SLC19A1 |
Zornitza Stark gene: SLC19A1 was added gene: SLC19A1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: SLC19A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC19A1 were set to 32276275 Phenotypes for gene: SLC19A1 were set to Megaloblastic anemia, folate-responsive, MIM# 601775 Review for gene: SLC19A1 was set to RED Added comment: Single individual reported with in-frame deletion, some functional data. Sources: Expert list |
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| Mendeliome v0.7166 | SMPD1 |
Zornitza Stark changed review comment from: Well established gene-disease association.; to: Niemann-Pick disease (NPD) refers to a group of disorders that present with varying degrees of lipid storage and foam cell infiltration in tissues, as well as overlapping clinical features including hepatosplenomegaly, pulmonary insufficiency and/or central nervous system (CNS) involvement. Type A NPD patients exhibit hepatosplenomegaly in infancy and profound CNS involvement. They rarely survive beyond 2-3years of age. Type B patients also have hepatosplenomegaly and pathologic alterations of their lungs, but there are usually no CNS signs. The age of onset and rate of disease progression varies greatly among type B patients, and they frequently live into adulthood. Intermediate patients also have been reported with mild to moderate neurological findings. Well established gene-disease association. |
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| Mendeliome v0.7150 | NAGA | Zornitza Stark Phenotypes for gene: NAGA were changed from Kanzaki disease (MIM # 609242); Schindler disease, type I or III (MIM# 609241) to Kanzaki disease, MIM# 609242; Schindler disease, type I and type II 609241; alpha-N-acetylgalactosaminidase deficiency MONDO:0017779 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7148 | NAGA | Zornitza Stark reviewed gene: NAGA: Rating: GREEN; Mode of pathogenicity: None; Publications: 11313741, 31468281, 15619430, 8782044; Phenotypes: Kanzaki disease, MIM# 609242, Schindler disease, type I and type II 609241, alpha-N-acetylgalactosaminidase deficiency MONDO:0017779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7072 | GALNS | Zornitza Stark Marked gene: GALNS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7072 | GALNS | Zornitza Stark Gene: galns has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7072 | GALNS | Zornitza Stark Phenotypes for gene: GALNS were changed from to Mucopolysaccharidosis IVA, MIM# 253000; MONDO:0009659 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7071 | GALNS | Zornitza Stark Publications for gene: GALNS were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7070 | GALNS | Zornitza Stark Mode of inheritance for gene: GALNS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7069 | GALNS | Zornitza Stark reviewed gene: GALNS: Rating: GREEN; Mode of pathogenicity: None; Publications: 9298823; Phenotypes: Mucopolysaccharidosis IVA, MIM# 253000, MONDO:0009659; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7069 | GALC | Zornitza Stark Marked gene: GALC as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7069 | GALC | Zornitza Stark Gene: galc has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7069 | GALC | Zornitza Stark Phenotypes for gene: GALC were changed from to Krabbe disease, MIM# 245200; MONDO:0009499 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7068 | GALC | Zornitza Stark Publications for gene: GALC were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7067 | GALC | Zornitza Stark Mode of inheritance for gene: GALC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7066 | GALC | Zornitza Stark reviewed gene: GALC: Rating: GREEN; Mode of pathogenicity: None; Publications: 20886637; Phenotypes: Krabbe disease, MIM# 245200, MONDO:0009499; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7017 | CARD9 | Zornitza Stark Phenotypes for gene: CARD9 were changed from to Candidiasis, familial, 2, autosomal recessive, MIM# 212050; Predisposition to invasive fungal disease, MONDO:0008905 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.7014 | CARD9 | Zornitza Stark reviewed gene: CARD9: Rating: GREEN; Mode of pathogenicity: None; Publications: 19864672, 23335372, 24131138, 33789983, 33558980, 33180249; Phenotypes: Candidiasis, familial, 2, autosomal recessive, MIM# 212050, Predisposition to invasive fungal disease, MONDO:0008905; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6850 | CHRDL1 | Zornitza Stark Phenotypes for gene: CHRDL1 were changed from to Megalocornea OMIM# 309300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6847 | CHRDL1 | Zornitza Stark reviewed gene: CHRDL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25093588; Phenotypes: Megalocornea OMIM# 309300; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6552 | KIDINS220 | Zornitza Stark Phenotypes for gene: KIDINS220 were changed from to Spastic paraplegia, intellectual disability, nystagmus, and obesity, MIM# 617296; cerebral ventriculomegaly; limb contractures | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6539 | KIDINS220 | Eleanor Williams reviewed gene: KIDINS220: Rating: AMBER; Mode of pathogenicity: None; Publications: 33205811, 28934391, 22048169; Phenotypes: cerebral ventriculomegaly, limb contractures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6446 | GALNT12 | Bryony Thompson Marked gene: GALNT12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6446 | GALNT12 | Bryony Thompson Gene: galnt12 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6446 | GALNT12 | Bryony Thompson Classified gene: GALNT12 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6446 | GALNT12 | Bryony Thompson Gene: galnt12 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6445 | GALNT12 | Bryony Thompson reviewed gene: GALNT12: Rating: RED; Mode of pathogenicity: None; Publications: 19617566, 30523343, 29749045; Phenotypes: Colorectal cancer, susceptibility to, 1 MIM#608812; Mode of inheritance: Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6445 | C1GALT1C1 | Bryony Thompson Tag somatic tag was added to gene: C1GALT1C1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6321 | FCHO1 | Zornitza Stark Phenotypes for gene: FCHO1 were changed from Combined immunodeficiency; T cells: low, poor proliferation; B cells: normal number; Recurrent infections (viral, mycobacteria, bacterial, fungal); lymphoproliferation; Failure to thrive; Increased activation-induced T-cell death; Defective clathrin-mediated endocytosis to Immunodeficiency 76, MIM# 619164; Combined immunodeficiency; T cells: low, poor proliferation; B cells: normal number; Recurrent infections (viral, mycobacteria, bacterial, fungal); lymphoproliferation; Failure to thrive; Increased activation-induced T-cell death; Defective clathrin-mediated endocytosis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6320 | FCHO1 | Zornitza Stark edited their review of gene: FCHO1: Changed phenotypes: Immunodeficiency 76, MIM# 619164, Combined immunodeficiency, T cells: low, poor proliferation, B cells: normal number, Recurrent infections (viral, mycobacteria, bacterial, fungal), lymphoproliferation, Failure to thrive, Increased activation-induced T-cell death, Defective clathrin-mediated endocytosis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6228 | SLC46A1 | Zornitza Stark changed review comment from: Hereditary folate malabsorption is an autosomal recessive disorder characterized by signs and symptoms of folate deficiency that appear within a few months after birth. Infants exhibit low blood and cerebrospinal fluid folate levels with megaloblastic anemia, diarrhea, immune deficiency, infections, and neurologic deficits. Treatment with folate supplementation results in resolution of the signs and symptoms. The disorder is caused by impaired intestinal folate absorption and impaired transport of folate into the central nervous system. More than 5 unrelated families reported.; to: Hereditary folate malabsorption is an autosomal recessive disorder characterized by signs and symptoms of folate deficiency that appear within a few months after birth. Infants exhibit low blood and cerebrospinal fluid folate levels with megaloblastic anemia, diarrhoea, immune deficiency, infections, and neurologic deficits. Treatment with folate supplementation results in resolution of the signs and symptoms. The disorder is caused by impaired intestinal folate absorption and impaired transport of folate into the central nervous system. More than 5 unrelated families reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6228 | ST3GAL3 | Zornitza Stark Marked gene: ST3GAL3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6228 | ST3GAL3 | Zornitza Stark Gene: st3gal3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6228 | ST3GAL3 | Zornitza Stark Phenotypes for gene: ST3GAL3 were changed from to Mental retardation, autosomal recessive 12 MIM# 611090 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6227 | ST3GAL3 | Zornitza Stark Publications for gene: ST3GAL3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6226 | ST3GAL3 | Zornitza Stark Mode of inheritance for gene: ST3GAL3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6225 | ST3GAL3 | Zornitza Stark reviewed gene: ST3GAL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23252400, 21907012, 31584066; Phenotypes: Mental retardation, autosomal recessive 12 MIM# 611090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6174 | OTUD5 |
Zornitza Stark gene: OTUD5 was added gene: OTUD5 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: OTUD5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: OTUD5 were set to 33131077 Phenotypes for gene: OTUD5 were set to X-linked severe neurodevelopmental delay, hydrocephalus, and early lethality Review for gene: OTUD5 was set to RED Added comment: 13 male patients from a single family with three generations affected. Patients presented prenatally or during the neonatal period with IUGR, ventriculomegaly, hydrocephalus, hypotonia, congenital heart defects, hypospadias, and severe neurodevelopmental delay. The disease is typically fatal during infancy, mainly due to sepsis (pneumonias). Female carriers are asymptomatic. WGS in four individuals identified a unique candidate variant in the OTUD5 gene (NM_017602.3:c.598G > A, p.Glu200Lys). The variant cosegregated with the disease in 10 tested individuals. No functional studies. Sources: Literature |
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| Mendeliome v0.5956 | SLC5A1 | Zornitza Stark Phenotypes for gene: SLC5A1 were changed from to Glucose/galactose malabsorption, MIM# 606824 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5953 | SLC5A1 | Zornitza Stark reviewed gene: SLC5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20486940, 32946683; Phenotypes: Glucose/galactose malabsorption, MIM# 606824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5763 | SLC35D1 | Zornitza Stark Phenotypes for gene: SLC35D1 were changed from Schneckenbecken dysplasia, MIM 269250 to Schneckenbecken dysplasia, MIM 269250, MONDO:0010013; O-xylosyl/N-acetylgalactosaminylglycan synthesis deficiencies (Disorders of protein O-glycosylation) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5761 | SLC35D1 | Zornitza Stark reviewed gene: SLC35D1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17952091, 19508970, 31423530; Phenotypes: Schneckenbecken dysplasia 269250, O-xylosyl/N-acetylgalactosaminylglycan synthesis deficiencies (Disorders of protein O-glycosylation); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5739 | ST3GAL5 | Zornitza Stark Tag founder tag was added to gene: ST3GAL5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5739 | ST3GAL5 | Zornitza Stark Marked gene: ST3GAL5 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5739 | ST3GAL5 | Zornitza Stark Gene: st3gal5 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5739 | ST3GAL5 | Zornitza Stark Phenotypes for gene: ST3GAL5 were changed from to Salt and pepper developmental regression syndrome 609056; GM3 synthase deficiency, MONDO:0018274; Lactosylceramide alpha-2,3-sialyltransferase deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5738 | ST3GAL5 | Zornitza Stark Publications for gene: ST3GAL5 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5737 | ST3GAL5 | Zornitza Stark Mode of inheritance for gene: ST3GAL5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5736 | ST3GAL5 | Zornitza Stark reviewed gene: ST3GAL5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23436467, 22990144, 15502825, 27232954, 30691927, 30688114, 30576498; Phenotypes: Salt and pepper developmental regression syndrome 609056, GM3 synthase deficiency, MONDO:0018274, Lactosylceramide alpha-2,3-sialyltransferase deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5696 | B3GALT6 | Zornitza Stark Marked gene: B3GALT6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5696 | B3GALT6 | Zornitza Stark Gene: b3galt6 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5696 | B3GALT6 | Zornitza Stark Phenotypes for gene: B3GALT6 were changed from to Al-Gazali syndrome, MIM# 609465; Ehlers-Danlos syndrome, spondylodysplastic type, 2, MIM# 615349, MONDO:0014139; Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures, MIM# 271640, MONDO:0010075 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5695 | B3GALT6 | Zornitza Stark Publications for gene: B3GALT6 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5694 | B3GALT6 | Zornitza Stark Mode of inheritance for gene: B3GALT6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5693 | B3GALT6 | Zornitza Stark reviewed gene: B3GALT6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25149931, 29443383, 23664117, 29931299, 23664117, 23664118, 31614862; Phenotypes: Al-Gazali syndrome, MIM# 609465, Ehlers-Danlos syndrome, spondylodysplastic type, 2, MIM# 615349, MONDO:0014139, Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures, MIM# 271640, MONDO:0010075; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5693 | B3GALNT2 | Zornitza Stark Marked gene: B3GALNT2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5693 | B3GALNT2 | Zornitza Stark Gene: b3galnt2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5693 | B3GALNT2 | Zornitza Stark Phenotypes for gene: B3GALNT2 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11, MIM# 615181; MONDO:0014071 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5692 | B3GALNT2 | Zornitza Stark Publications for gene: B3GALNT2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5691 | B3GALNT2 | Zornitza Stark Mode of inheritance for gene: B3GALNT2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5690 | B3GALNT2 | Zornitza Stark reviewed gene: B3GALNT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23453667, 33290285, 29791932, 29273094, 28688748, 28303321; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11, MIM# 615181, MONDO:0014071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5567 | VPS4A |
Kristin Rigbye changed review comment from: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life." Sources: Literature; to: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life." |
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| Mendeliome v0.5567 | VPS4A |
Elena Savva changed review comment from: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."; to: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life." |
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| Mendeliome v0.5567 | VPS4A | Elena Savva Added comment: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life." | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5558 | VPS4A |
Kristin Rigbye gene: VPS4A was added gene: VPS4A was added to Mendeliome. Sources: Literature Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VPS4A were set to PMID: 33186543; 33186545 Phenotypes for gene: VPS4A were set to Neurodevelopmental disorder Review for gene: VPS4A was set to GREEN Added comment: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life." Sources: Literature |
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| Mendeliome v0.5553 | KDM4B |
Kristin Rigbye gene: KDM4B was added gene: KDM4B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: KDM4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KDM4B were set to PMID: 33232677 Phenotypes for gene: KDM4B were set to Global developmental delay, intellectual disability and neuroanatomical defects Review for gene: KDM4B was set to GREEN Added comment: Nine individuals with mono-allelic de novo or inherited variants in KDM4B. All individuals presented with dysmorphic features and global developmental delay (GDD) with language and motor skills most affected. Three individuals had a history of seizures, and four had anomalies on brain imaging ranging from agenesis of the corpus callosum with hydrocephalus to cystic formations, abnormal hippocampi, and polymicrogyria. In a knockout mouse the total brain volume was significantly reduced with decreased size of the hippocampal dentate gyrus, partial agenesis of the corpus callosum, and ventriculomegaly. Sources: Literature |
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| Mendeliome v0.5365 | B4GALT7 | Zornitza Stark Marked gene: B4GALT7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5365 | B4GALT7 | Zornitza Stark Gene: b4galt7 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5365 | B4GALT7 | Zornitza Stark Phenotypes for gene: B4GALT7 were changed from to Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5364 | B4GALT7 | Zornitza Stark Publications for gene: B4GALT7 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5363 | B4GALT7 | Zornitza Stark Mode of inheritance for gene: B4GALT7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5362 | B4GALT7 | Zornitza Stark Tag founder tag was added to gene: B4GALT7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5362 | B4GALT7 | Zornitza Stark reviewed gene: B4GALT7: Rating: GREEN; Mode of pathogenicity: None; Publications: 23956117, 24755949; Phenotypes: Ehlers-Danlos syndrome, spondylodysplastic type, 1, MIM# 130070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5357 | B4GALT7 | Elena Savva reviewed gene: B4GALT7: Rating: GREEN; Mode of pathogenicity: None; Publications: Ehlers-Danlos syndrome, spondylodysplastic type, 1, 130070; Phenotypes: PMID: 31278392, 31614862, 31862401; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5315 | ZFHX4 |
Bryony Thompson changed review comment from: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (5 frameshift, 5 missense, 4 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). Sources: Literature; to: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (5 frameshift, 5 missense, 4 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). PMID: 24038936 - a single case with developmental delay, macrocephaly, ventriculomegaly, hypermetropia, recurrent infections, dysmorphism and a de novo deletion of the last 7 exons of the gene. Sources: Literature |
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| Mendeliome v0.5191 | ALPK1 | Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5190 | ALPK1 | Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome ROSAH syndrome, MIM#614979 to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5189 | ALPK1 | Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome ROSAH syndrome, MIM#614979 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.5188 | ALPK1 | Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndromeROSAH syndrome, MIM#614979 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4837 | LTBP2 | Zornitza Stark Phenotypes for gene: LTBP2 were changed from to Glaucoma 3, primary congenital, D 613086; Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, MIM# 251750 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4834 | LTBP2 | Zornitza Stark reviewed gene: LTBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19656777, 19361779, 20617341, 32165823, 30380740, 30565850; Phenotypes: Glaucoma 3, primary congenital, D 613086, Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, MIM# 251750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4520 | SLC12A2 |
Zornitza Stark edited their review of gene: SLC12A2: Added comment: Monoallelic : DD/ID was a feature in >= 6 individuals with monoallelic de novo SLC12A2. An individual with an exon 22 truncating variant was reported to have normal milestones and cognitive function. Exon 21 variants have been described in individuals with rather isolated hearing impairment (possibly some associated motor delay, but normal cognition). Hearing impairment was also reported in 2/6 patients with variants in other exons (1 missense / 1 frameshift). Biallelic : DD/ID was reported in at least 3 individuals in literature. Hearing impairment has been reported on 2 occasions (although this was not probably evaluated in all subjects). --- Monoallelic SLC12A2 mutations : ► Individuals with de novo mutations and developmental disorder were first identified by the DDD study (2017 - PMID: 28135719). 5 of them have been reported in detail by McNeill et al (below). ► McNeill et al (2020 - PMID: 32658972) report on 6 individuals with neurodevelopmental disorder due to de novo SLC12A2 mutation. All presented DD or ID ranging from mild to severe. ASD was reported in 3/6. Sensorineural hearing loss was a feature in 2/6 with the remaining having normal formal evaluations. Brain, cardiac and/or additional malformations were reported in a single individual. Following non-diagnostic prior work-up (CMA, FMR1 or other investigations) trio exome sequencing revealed missense (4/6) or truncating variants (2/6). Three additional individuals (incl. a father and his son) with missense variants in exon 21 (NM_001046.3 / p.Glu979Lys and p.Glu980Lys) presented with bilateral sensorineural hearing loss. Speech and/or motor delay reported in these cases were attributed to the hearing impairment/vestibular arreflexia (cognitive abilities not tested). SLC12A2 encodes sodium-potassium-chloride transporter 1 (also NKCC1). The GTEx project has identified 8 isoforms. In brain both exon 21-containing/deleted isoforms are expressed (cited Morita et al 2014 - PMID: 24695712). As the authors discuss, RNA-seq of the developing mouse cochlea suggests that the exon 21 containing isoform is the single transcript expressed. Evidence from RNA-seq data (BrainSpan project) and literature suggests that the significant amounts of exon 21 lacking isoforms in fetal brain compensate for the deleterious effects of exon 21 variants and explain the lack of NDD in relevant patients. Slc12a2 (NKCC1) null mouse model has demonstrated that the transporter plays a role in accumulation of the potassium rich endolymph in the inner ear, with NKCC1 absence causing sensorineural deafness and imbalance. Slc12a2 display cochlear malformations, loss of hair cells and hearing impairment (cited Delpire et al 1999 - PMID: 10369265). The brain phenotype has not been studied extensively, although loss of Slc12a2 has been shown to inhibit neurogenesis (cited: Magalhães and Rivera et al. - PMID: 27582690). Slc12a2 null zebrafish display a collapse of the otic vesicle and reduced endolymph (Abbas and Whitfield, 2009 - PMID: 19633174) relevant to the human hearing disorder. In vitro assessment of NKCC1 ion transporter function in Xenopus laevis, supported the deleterious effect of the identified variants (significant reduction in K+ influx). Using available single cell RNA-seq data the authors further demonstrated that SLC12A2 expressing cells display transcriptomic profiles reflective of active neurogenesis. ► Delpire et al (2016 - PMID: 27900370 - not reviewed in detail) described a 13 y.o. girl harboring a de novo 11-bp deletion in SLC12A2 exon 22. This individual reached developmental milestones on time and had a NORMAL cognitive function. Hearing was seemingly normal. Features included orthostatic intolerance, respiratory weakness, multiple endocrine abnormalities, pancreatic insufficiency and multiorgan failure incl. gut and bladder. Exome in the proband, parents and 3 unaffected sibs suggested SLC12A2 as the only candidate for her phenotype. Functional analyses in Xenopus laevis oocytes suggested that a non functional transporter was expressed and trafficked to the membrane as the wt. Detection of the truncated protein at higher molecular sizes suggested either enhanced dimerization or misfolded aggregate. There was no dominant-negative effect of mutant NKCC1. In patient fibroblasts a reduced total and NKCC1-mediated K+ influx. ► Mutai et al (2020 - PMID: 32294086) report on several individuals from 4 families, harboring variants within exon 21 or - in one case - at it's 3' splice-site (leading to skipping oe this exon at the mRNA level). All subjects were investigated for severe/profound hearing loss (in line with the role of exon 21-included isoforms in cochlea. The variant segregated with hearing impairment in 3 generations of a family while in all other subjects the variant had occured as de novo event. Despite motor delays (e.g. the subject from fam2 could not hold head or sit at the age of 10m / the proband in Fam3 was able to hold his head and walk at 6 and 20 m respectively) behavior and cognition were commented to be within normal range. ----- Biallelic SLC12A2 mutations: ► Anazi et al (2017 - PMID: 29288388) briefly reported on a 3 y.o. boy (17DG0776) with central hypotonia, neonatal respiratory distress, failure to thrive, global DD and microcephaly and a skeletal survey suggestive of osteopenia. After non-diagnostic prior investigations (CMA revealing a 1p duplication classified as VUS, extensive metabolic workup), WES revealed a homozygous SLC12A2 splicing variant [NM_001046.2:c.2617-2A>G]. ► Macnamara et al (2019 - PMID: 30740830) described a 5.5 y.o. male with sensorineural hearing loss, profound delays in all developmental areas among several other features (choanal atresia, failure to thrive, respiratory problems, absent sweat and tear production or salivation, GI abnormalities). Genetic testing for several disorders considered (cystic fibrosis, spinal muscular atrophy, sequencing and del/dup analysis of mtDNA) was normal. CMA revealed paternal uniparental isodisomy for chr. 5 and WGS a homozygous 22kb deletion in SLC12A2. This was followed by confirmation of homozygosity in the proband, heterozygosity of the unaffected father, delineation of breakpoints (chr5:127441491-127471419). mRNA studies in patient fibroblasts confirmed deletion of ex2-7, splicing of ex1 directly to ex8 and introduction of a premature stop codon in ex9. qRT-PCR confirmed that mRNA is likely subjected to NMD (expression ~80% of control). Western blot confirmed absence of the protein in the patient's fibroblasts. Again mouse models are thought to recapitulate the hearing defect but also the deficient saliva production (cited Evans et al 2000 - PMID: 10831596). Again the authors speculate a role of SLC12A2 in brain development based on evidence from murine models (migration, dendritic growth, increse in neuron density through regulation of GABAergic signalling (Young et al 2012 - PMID: 23015452). Hypotheses are also made on a regulatory relationship between NKCC1 and CFTR based on mRNA data from the ko mouse model. ► Stödberg et al (2020 - PMID: 32754646) reported 2 sibs with a complex neurodevelopmental disorder due to compound heterozygosity for a frameshift SLC12A2 variant and a splicing one (NM_001046:c.1431delT and c.2006-1G>A). Both presented hypotonia, neonatal S. aureus parotitis and respiratory problems (incl. apneas). While the older sib died at the age of 22 days, the younger one had persistent respiratory issues incl. a dry respiratory mucosa motivating metabolic, immunology investigations and testing for CF. She displayed microcephaly (OFC -2.5 SD, H was also -3.5SD), severe intellectual disability. MRI was suggestive of white matter and basal ganglia abnormalities. Other features incl. hearing impairment, and lack of tears,saliva and sweat, constipation and intestinal malrotation. There was facial dysmorphism. The variants were the only retained following WGS of the 2 affected sisters, parents and an unaffected brother. The splicing variant was shown to result in skipping of exon 13, while the indel in NMD. Again the authors discuss that the deficient saliva production, impaired hearing and GI problems are recapitulated in the mouse model (several refs provided).; Changed rating: GREEN; Changed publications: 28135719, 32658972, 27900370, 32294086, 29288388, 30740830, 32754646; Changed phenotypes: Kilquist syndrome, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Mendeliome v0.4434 | SLC19A2 | Zornitza Stark Phenotypes for gene: SLC19A2 were changed from to Thiamine-responsive megaloblastic anemia syndrome, MIM# 249270 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4431 | SLC19A2 | Zornitza Stark reviewed gene: SLC19A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10391221, 10978358; Phenotypes: Thiamine-responsive megaloblastic anemia syndrome, MIM# 249270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4229 | TET2 | Zornitza Stark changed review comment from: PMID 32518946: 3 children with an immune dysregulation syndrome of susceptibility to infection, lymphadenopathy, hepatosplenomegaly, developmental delay, autoimmunity, and lymphoma of B-cell (n = 2) or T-cell (n = 1) origin, and bi-allelic variants in TET2.; to: Bi-allelic variants PMID 32518946: 3 children with an immune dysregulation syndrome of susceptibility to infection, lymphadenopathy, hepatosplenomegaly, developmental delay, autoimmunity, and lymphoma of B-cell (n = 2) or T-cell (n = 1) origin, and bi-allelic variants in TET2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4229 | TET2 | Zornitza Stark edited their review of gene: TET2: Added comment: PMID 32518946: 3 children with an immune dysregulation syndrome of susceptibility to infection, lymphadenopathy, hepatosplenomegaly, developmental delay, autoimmunity, and lymphoma of B-cell (n = 2) or T-cell (n = 1) origin, and bi-allelic variants in TET2.; Changed rating: GREEN; Changed publications: 30890702, 31827242, 32330418, 32518946; Changed phenotypes: Dementia, Lymphoma/myeloid malignancy, Immunodeficiency; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4214 | TPRKB | Zornitza Stark Phenotypes for gene: TPRKB were changed from to Galloway-Mowat syndrome 5, MIM# 617731 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4211 | TPRKB | Zornitza Stark reviewed gene: TPRKB: Rating: GREEN; Mode of pathogenicity: None; Publications: 28805828, 30053862; Phenotypes: Galloway-Mowat syndrome 5, MIM# 617731; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4211 | TP53RK | Zornitza Stark Phenotypes for gene: TP53RK were changed from to Galloway-Mowat syndrome 4, MIM# 617730 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4208 | TP53RK | Zornitza Stark reviewed gene: TP53RK: Rating: GREEN; Mode of pathogenicity: None; Publications: 28805828, 30053862; Phenotypes: Galloway-Mowat syndrome 4, MIM# 617730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4058 | YRDC |
Zornitza Stark gene: YRDC was added gene: YRDC was added to Mendeliome. Sources: Literature Mode of inheritance for gene: YRDC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YRDC were set to 31481669 Phenotypes for gene: YRDC were set to Galloway-Mowat syndrome Review for gene: YRDC was set to GREEN Added comment: Three individuals from two unrelated families with typical features of Galloway-Mowat syndrome including proteinuria, microcephaly, developmental delay and brain malformations. Supportive functional data. Sources: Literature |
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| Mendeliome v0.4056 | GON7 |
Zornitza Stark gene: GON7 was added gene: GON7 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GON7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GON7 were set to 31481669 Phenotypes for gene: GON7 were set to Galloway-Mowat syndrome Review for gene: GON7 was set to GREEN Added comment: 11 individuals from 5 families. Four of the families had the same homozygous variant, shared haplotype suggestive of founder effect. Clinical features included proteinuria, microcephaly, brain malformations and developmental delay. Supportive functional data. Sources: Literature |
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| Mendeliome v0.4055 | LAGE3 | Zornitza Stark Phenotypes for gene: LAGE3 were changed from to Galloway-Mowat syndrome 2, X-linked, MIM# 301006 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4052 | LAGE3 | Zornitza Stark reviewed gene: LAGE3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28805828; Phenotypes: Galloway-Mowat syndrome 2, X-linked, MIM# 301006; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4048 | OSGEP | Zornitza Stark Phenotypes for gene: OSGEP were changed from to Galloway-Mowat syndrome 3, MIM# 617729 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4045 | OSGEP | Zornitza Stark reviewed gene: OSGEP: Rating: GREEN; Mode of pathogenicity: None; Publications: 28805828, 28272532; Phenotypes: Galloway-Mowat syndrome 3, MIM# 617729; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4045 | NUP107 | Zornitza Stark Phenotypes for gene: NUP107 were changed from to Galloway-Mowat syndrome 7, MIM# 618348 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4042 | NUP107 | Zornitza Stark reviewed gene: NUP107: Rating: GREEN; Mode of pathogenicity: None; Publications: 28280135, 28117080, 30179222, 25558065; Phenotypes: Galloway-Mowat syndrome 7, MIM# 618348; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3993 | A4GALT | Zornitza Stark Marked gene: A4GALT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3993 | A4GALT | Zornitza Stark Gene: a4galt has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3993 | A4GALT | Zornitza Stark Phenotypes for gene: A4GALT were changed from to [Blood group, P1Pk system, p phenotype], MIM# 111400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3992 | A4GALT | Zornitza Stark Classified gene: A4GALT as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3992 | A4GALT | Zornitza Stark Gene: a4galt has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3991 | A4GALT | Zornitza Stark reviewed gene: A4GALT: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: [Blood group, P1Pk system, p phenotype], MIM# 111400; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3049 | FAN1 | Elena Savva reviewed gene: FAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22772369; Phenotypes: Interstitial nephritis, karyomegalic 614817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2943 | TRIM71 |
Elena Savva gene: TRIM71 was added gene: TRIM71 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TRIM71 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TRIM71 were set to PMID: 29983323; 32168371; 30975633 Phenotypes for gene: TRIM71 were set to Hydrocephalus, congenital communicating, 1 618667 Mode of pathogenicity for gene: TRIM71 was set to Other Added comment: PMID: 29983323 - 3 unrelated patients with de novo missense and hydrocephalus with ventriculomegaly (p.Arg608His recurrent). One patient then transmitted the variant to an affected child. PMID: 32168371 - refers to the gene as an established sources of neurodevelopmental disorder PMID: 30975633 - identifies and proves by functional studies that TRIM71 is essential for neurodevelopment. Proposes a LOF mechanism. Sources: Literature |
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| Mendeliome v0.2649 | CTSA | Zornitza Stark Phenotypes for gene: CTSA were changed from to Galactosialidosis, MIM# 256540; Cathepsin A-related arteriopathy with strokes and leukoencephalopathy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2635 | CTSA | Zornitza Stark changed review comment from: Bi-allelic variants cause galactosialidosis, and mono-allelic variants cause CARASAL.; to: Bi-allelic variants associated with galactosialidosis, and mono-allelic variants associated with CARASAL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2635 | CTSA | Zornitza Stark reviewed gene: CTSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31177426; Phenotypes: Galactosialidosis, MIM# 256540, Cathepsin A-related arteriopathy with strokes and leukoencephalopathy; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2629 | ALPK1 | Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2625 | ALPK1 | Zornitza Stark edited their review of gene: ALPK1: Added comment: Six unrelated families reported with same recurrent missense variant c.710C>T, (p.Thr237Met) and ROSAH syndrome phenotype. Pancytopaenia and recurrent infections present in some.; Changed rating: GREEN; Changed publications: 31053777, 30967659, 31939038; Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, ROSAH syndrome, retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2622 | GALM | Zornitza Stark Marked gene: GALM as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2622 | GALM | Zornitza Stark Gene: galm has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2622 | GALM | Zornitza Stark Classified gene: GALM as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2622 | GALM | Zornitza Stark Gene: galm has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2620 | GALM |
Hazel Phillimore gene: GALM was added gene: GALM was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GALM were set to PMID: 30451973; 30910422 Phenotypes for gene: GALM were set to galactosaemia; type IV galactosaemia Review for gene: GALM was set to GREEN Added comment: Homozygous and compound heterozygous variants (missense, nonsense and frameshift) found in 8 Japanese patients from unrelated families with unexplained galactosaemia. (No variants in GALT, GALK1, and GALE). This is therefore type IV galactosaemia. In vitro expression analysis and enzyme activity assay of the patients’ peripheral blood mononuclear cells showed total lack of or compromised expression of GALM protein. Loss-of-function mechanism. One homozygote for one of these variants p.(Gly142Arg) in gnomAD (African population). (Wada, Y. et al 2019; PMID: 30451973) In vitro expression assay and an enzyme activity assay of 67 GALM variants, taken from ExAc database (missense, nonsense, frameshift and splice). 30 variants concluded to be pathogenic due to no protein expression or faint expression. 5 variants with mildly lower levels were determined as likely pathogenic. All concluded to be loss-of-function mechanism. Incidence of galactosaemia by GALM deficiency is comparable to that of other galactosaemias. Carrier frequency and incidence was estimated for different populations. (Iwasawa, S. et al. (2019); PMID: 30910422) Sources: Literature |
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| Mendeliome v0.2580 | CSGALNACT1 | Zornitza Stark Publications for gene: CSGALNACT1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2579 | CSGALNACT1 | Zornitza Stark reviewed gene: CSGALNACT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31705726, 31325655; Phenotypes: Congenital disorder of glycosylation, skeletal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2549 | GALNT2 | Zornitza Stark Classified gene: GALNT2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2549 | GALNT2 | Zornitza Stark Gene: galnt2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2548 | GALNT2 |
Zornitza Stark gene: GALNT2 was added gene: GALNT2 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GALNT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GALNT2 were set to 32293671 Phenotypes for gene: GALNT2 were set to Congenital disorder of glycosylation Review for gene: GALNT2 was set to GREEN Added comment: Seven individuals from four families reported with bi-allelic LOF variants and global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities. Sources: Literature |
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| Mendeliome v0.2372 | MYCN | Zornitza Stark Phenotypes for gene: MYCN were changed from to Feingold syndrome 1; megalencephaly; ventriculomegaly; hypoplastic corpus callosum; intellectual disability; polydactyly; neuroblastoma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2361 | MYCN | Ain Roesley reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21224895, 8470948, 30573562; Phenotypes: Feingold syndrome 1, megalencephaly, ventriculomegaly, hypoplastic corpus callosum, intellectual disability, polydactyly, neuroblastoma; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2361 | MYCN | Ain Roesley edited their review of gene: MYCN: Added comment: PMID: 30573562; case report of an individual with a missense in MYCN with functional studies done in neuronal progenitor/stem cells demonstrating gain-of-function; Changed rating: RED; Changed publications: PMID: 30573562; Changed phenotypes: megalencephaly, ventriculomegaly, hypoplastic corpus callosum, intellectual disability, polydactyly, neuroblastoma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1944 | IL2RB |
Zornitza Stark gene: IL2RB was added gene: IL2RB was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: IL2RB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL2RB were set to 31040184; 31040185 Phenotypes for gene: IL2RB were set to Immunodeficiency 63 with lymphoproliferation and autoimmunity, MIM# 618495; Lymphoproliferation, lymphadenopathy, hepatosplenomegaly, autoimmune haemolytic anaemia, dermatitis, enteropathy, hypergammaglobulinaemia, recurrent viral (EBV, CMV) infections Review for gene: IL2RB was set to GREEN Added comment: Five families reported. Sources: Expert list |
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| Mendeliome v0.1914 | FCHO1 |
Zornitza Stark gene: FCHO1 was added gene: FCHO1 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: FCHO1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FCHO1 were set to 32098969; 30822429 Phenotypes for gene: FCHO1 were set to Combined immunodeficiency; T cells: low, poor proliferation; B cells: normal number; Recurrent infections (viral, mycobacteria, bacterial, fungal); lymphoproliferation; Failure to thrive; Increased activation-induced T-cell death; Defective clathrin-mediated endocytosis Review for gene: FCHO1 was set to GREEN Added comment: More than 10 affected individuals with bi-allelic variants in this gene reported. Functional data. Sources: Expert list |
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| Mendeliome v0.1679 | RPS23 | Zornitza Stark Phenotypes for gene: RPS23 were changed from to Brachycephaly, trichomegaly, and developmental delay, MIM# 617412 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1674 | RPS23 | Zornitza Stark reviewed gene: RPS23: Rating: AMBER; Mode of pathogenicity: None; Publications: 28257692; Phenotypes: Brachycephaly, trichomegaly, and developmental delay, MIM# 617412; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1537 | TBC1D7 | Zornitza Stark Phenotypes for gene: TBC1D7 were changed from to Macrocephaly/megalencephaly syndrome, autosomal recessive, MIM# 248000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1533 | TBC1D7 | Zornitza Stark reviewed gene: TBC1D7: Rating: AMBER; Mode of pathogenicity: None; Publications: 24515783, 23687350; Phenotypes: Macrocephaly/megalencephaly syndrome, autosomal recessive, MIM# 248000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1345 | CSGALNACT1 | Tiong Tan Marked gene: CSGALNACT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1345 | CSGALNACT1 | Tiong Tan Gene: csgalnact1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1345 | CSGALNACT1 | Tiong Tan Classified gene: CSGALNACT1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1345 | CSGALNACT1 | Tiong Tan Gene: csgalnact1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1344 | CSGALNACT1 |
Tiong Tan gene: CSGALNACT1 was added gene: CSGALNACT1 was added to Mendeliome. Sources: Expert Review,Literature Mode of inheritance for gene: CSGALNACT1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CSGALNACT1 were set to Congenital disorders of glycosylation; skeletal dysplasia; advanced bone age Review for gene: CSGALNACT1 was set to GREEN Added comment: Two unrelated families and functional studies Sources: Expert Review, Literature |
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| Mendeliome v0.717 | DNASE2 |
Zornitza Stark gene: DNASE2 was added gene: DNASE2 was added to Mendeliome_VCGS. Sources: Expert list Mode of inheritance for gene: DNASE2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DNASE2 were set to 29259162; 31775019 Phenotypes for gene: DNASE2 were set to Auto-inflammatory disorder; splenomegaly; glomerulonephritis; liver fibrosis; arthritis; HLH Review for gene: DNASE2 was set to GREEN Added comment: Inflammatory disorder characterized by splenomegaly, glomerulonephritis, liver fibrosis, circulating anti-DNA autoantibodies, and progressive arthritis. Three families and functional data. Sources: Expert list |
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| Mendeliome v0.308 | PISD | Zornitza Stark commented on gene: PISD: 4 individuals in 2 unrelated but consanguineous families from Portugal and Brazil affected by early-onset retinal degeneration, sensorineural hearing loss, microcephaly, intellectual disability, and skeletal dysplasia with scoliosis and short stature (Liberfarb syndrome). Affected individuals shared a homozygous 10-bp deletion immediately upstream of the last exon of the PISD gene. In HEK293T cells, this variant led to aberrant splicing of PISD transcripts. 1 family with 2 sisters with congenital cataracts, short stature, and white matter changes identified compound heterozygous variants in the PISD gene. Decreased conversion of phosphatidylserine to PE in patient fibroblasts is consistent with impaired phosphatidylserine decarboxylase (PISD) enzyme activity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.0 | ST3GAL5 |
Zornitza Stark gene: ST3GAL5 was added gene: ST3GAL5 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ST3GAL5 was set to Unknown |
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| Mendeliome v0.0 | ST3GAL3 |
Zornitza Stark gene: ST3GAL3 was added gene: ST3GAL3 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ST3GAL3 was set to Unknown |
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| Mendeliome v0.0 | GALT |
Zornitza Stark gene: GALT was added gene: GALT was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: GALT was set to Unknown |
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| Mendeliome v0.0 | GALNT3 |
Zornitza Stark gene: GALNT3 was added gene: GALNT3 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: GALNT3 was set to Unknown |
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| Mendeliome v0.0 | GALNT12 |
Zornitza Stark gene: GALNT12 was added gene: GALNT12 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: GALNT12 was set to Unknown |
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| Mendeliome v0.0 | GALNS |
Zornitza Stark gene: GALNS was added gene: GALNS was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: GALNS was set to Unknown |
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| Mendeliome v0.0 | GALK1 |
Zornitza Stark gene: GALK1 was added gene: GALK1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: GALK1 was set to Unknown |
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| Mendeliome v0.0 | GALE |
Zornitza Stark gene: GALE was added gene: GALE was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: GALE was set to Unknown |
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| Mendeliome v0.0 | GALC |
Zornitza Stark gene: GALC was added gene: GALC was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: GALC was set to Unknown |
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| Mendeliome v0.0 | C1GALT1C1 |
Zornitza Stark gene: C1GALT1C1 was added gene: C1GALT1C1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: C1GALT1C1 was set to Unknown |
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| Mendeliome v0.0 | B4GALT7 |
Zornitza Stark gene: B4GALT7 was added gene: B4GALT7 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: B4GALT7 was set to Unknown |
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| Mendeliome v0.0 | B4GALT1 |
Zornitza Stark gene: B4GALT1 was added gene: B4GALT1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: B4GALT1 was set to Unknown |
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| Mendeliome v0.0 | B4GALNT1 |
Zornitza Stark gene: B4GALNT1 was added gene: B4GALNT1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: B4GALNT1 was set to Unknown |
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| Mendeliome v0.0 | B3GALT6 |
Zornitza Stark gene: B3GALT6 was added gene: B3GALT6 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: B3GALT6 was set to Unknown |
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| Mendeliome v0.0 | B3GALNT2 |
Zornitza Stark gene: B3GALNT2 was added gene: B3GALNT2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: B3GALNT2 was set to Unknown |
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| Mendeliome v0.0 | B3GALNT1 |
Zornitza Stark gene: B3GALNT1 was added gene: B3GALNT1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: B3GALNT1 was set to Unknown |
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| Mendeliome v0.0 | A4GALT |
Zornitza Stark gene: A4GALT was added gene: A4GALT was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: A4GALT was set to Unknown |
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