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| Renal Tubulopathies and related disorders v2.2 | EGFR |
chirag patel edited their review of gene: EGFR: Added comment: Total 27 individuals from 24 families reported with this condition. 23 families (20 Roma descent, 3 unknown ethnicity) had the same homozygous missense variant in EGFR (c.1283 G>A; p.Gly428Asp) strongly supporting a founder effect. 1 Japanese family had compound heterozygous variants (p.R98X and p.I365N). Segregation testing was only performed in a few families. Condition characterised by intrauterine growth retardation, premature birth, skin issues (thin, translucent, fragile, desquamation, ichthyosis, infective/inflammatory lesions), nephromegaly, renal tubular dysfunction with electrolyte imbalances, chronic diarrhoea, necrotising enterocolitis, recurrent infections with sepsis, cardiac anomalies, and dysmorphism. Most die within 2.5 years. PMID 24691054: Skin biopsy demonstrated an altered cellular distribution of EGFR in the epidermis with reduced cell membrane labeling, and in vitro analysis of the mutant receptor revealed abrogated EGFR phosphorylation and EGF-stimulated downstream signaling. PMID 26436111: EGF failed to induce mutated receptor phosphorylation in patient-derived fibroblasts and activation of downstream targets was suppressed. The heterologously expressed extracellular domain was impaired in stability and the binding of EGF. EGFR knockout mice show some clinical and pathological similarities with patients though features are not present at birth but develop afterwards in the skin, lungs, and digestive organs (PMID 9176390, 7618085, 7630400).; Changed rating: GREEN; Changed publications: 24691054,36017778,26436111,32250467,32602142,40040597,29899996,9176390,7618085,7630400; Changed phenotypes: Inflammatory skin and bowel disease, neonatal 2, MONDO:0014481 |
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| Renal Tubulopathies and related disorders v2.0 | AIRE | Gene migrated from ENSG00000160224 to ENSG00000160224 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Tubulopathies and related disorders v1.0 | OXGR1 |
Sarah Pantaleo gene: OXGR1 was added gene: OXGR1 was added to Renal Tubulopathies and related disorders. Sources: Literature Mode of inheritance for gene: OXGR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: OXGR1 were set to PMID:35671463 Phenotypes for gene: OXGR1 were set to Nephrolithiasis/nephrocalcinosis Penetrance for gene: OXGR1 were set to unknown Review for gene: OXGR1 was set to AMBER Added comment: Candidate disease gene for human calcium oxalate nephrolithiasis. Performed exome sequencing and directed sequencing of the OXGR1 locus in a worldwide nephrolithiasis/nephrocalcinosis (NL/NC) cohort, and putatively deleterious rare OXGR1 variants were functionally characterised. A heterozygous OXGR1 missense variant (c.371T>G; p.Leu124Arg) co-segregated with calcium oxalate NL and/or NC disease in an autosomal dominant inheritance pattern within a multi-generational family with five affected individuals. Interrogation of the OXGR1 locus in 1,107 additional NL/NC families identified five additional deleterious dominant variants in five families with calcium oxalate NL/NC. Rare, potentially deleterious OXGR1 variants were enriched in NL/NC subjects relative to ExAC controls. Four missense variants and one frameshift variant. Four of five NL/NC-associated missense variants revealed impaired AKG-dependent calcium ion uptake, demonstrating loss of function. Rare, dominant loss-of-function OXGR1 variants are associated with recurrent calcium oxalate NL/NC disease. Six potentially deleterious variants were identified in six of 1,108 NL/NC families (0.54%). Limitations: only probands were able to be recruited for four of six families. In the future, it will be important to determine whether any of the affected family members share the identified OXGR1 variant. They also observe OXGR1 variants in 0.16% of ExAC subjects (selected on the basis of the absence of paediatric disease). Sources: Literature |
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| Renal Tubulopathies and related disorders v1.0 | AIRE | Zornitza Stark Marked gene: AIRE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Tubulopathies and related disorders v1.0 | AIRE | Zornitza Stark Gene: aire has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Tubulopathies and related disorders v0.4 | AIRE |
Zornitza Stark gene: AIRE was added gene: AIRE was added to Renal Tubulopathies and related disorders. Sources: Expert list,Expert Review Green Mode of inheritance for gene: AIRE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AIRE were set to 35521792 Phenotypes for gene: AIRE were set to Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia, OMIM #240300 |
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