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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 | RET | Gene migrated from ENSG00000165731 to ENSG00000165731 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal Tubulopathies and related disorders v1.19 | TFCP2L1 |
Zornitza Stark gene: TFCP2L1 was added gene: TFCP2L1 was added to Renal Tubulopathies and related disorders. Sources: Literature Mode of inheritance for gene: TFCP2L1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TFCP2L1 were set to 40569305; 33097957 Phenotypes for gene: TFCP2L1 were set to CAKUT, MONDO:0019719, TFGP2L1-related Review for gene: TFCP2L1 was set to AMBER Added comment: PMID 40569305: consanguineous preterm male infant with a clinical picture of advanced kidney dysfunction and severe renal salt-wasting, highly suggestive of prenatal onset Bartter syndrome. Patient's follow-up was characterized by severe polyuria; episodes of hyponatremia, hypokalemia, and hypochloremia; and metabolic alkalosis and hyperuricemia. Homozygous variant in the TFCP2L1 gene identified. TFCP2L1 is a transcription factor required for normal kidney development, that regulates acid-base and salt-water homeostasis. PMID 33097957: infant who developed CKD by the age of 2 months and had episodes of severe hypochloraemic, hyponatraemic and hypokalaemic alkalosis, seizures, developmental delay and hypotonia together with cataracts. Homozygous LoF variant. TFCP2L1 is localized throughout kidney development particularly in the distal nephron. TFCP2L1 induced the growth and development of renal tubules from rat mesenchymal cells. Conversely, the deletion of TFCP2L1 in mice was previously shown to lead to reduced expression of renal cell markers including ion transporters and cell identity proteins expressed in different segments of the distal nephron. TFCP2L1 localized to the nucleus in HEK293T cells only upon coexpression with its paralog upstream-binding protein 1 (UBP1). A TFCP2L1 mutant complementary DNA (cDNA) clone that represented the patient's mutation failed to form homo- and heterodimers with UBP1, an essential step for its transcriptional activity. Sources: Literature |
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| Renal Tubulopathies and related disorders v1.3 | SLC6A6 |
Zornitza Stark gene: SLC6A6 was added gene: SLC6A6 was added to Renal Tubulopathies and related disorders. Sources: Literature Mode of inheritance for gene: SLC6A6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SLC6A6 were set to 35115415; 21170874; 32660969 Phenotypes for gene: SLC6A6 were set to Primary hyperoxaluria, MONDO:0002474, SLC26A6-related Review for gene: SLC6A6 was set to RED Added comment: Cornière et al. 2022 (PMID: 35115415) identified a single family with a heterozygous missense VUS (c.1519C>T/p.R507W) in the SLC26A6 gene. However, the variant was found in 5 out of 280 674 alleles reported in gnomAD (Europeans and South Asians). In vitro studies showed that the variant affects both SLC26A6 transport activity and membrane surface expression, in turn reducing Cl− dependant oxalate transport. Cotransfection studies indicated a dominant-negative effect on WT. Slc26a6 null mice similarly displayed hyperoxalemia and hyperoxaluria which were caused by defective intestinal back-secretion of dietary oxalate (PMID: 21170874; 32660969) Sources: Literature |
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| Renal Tubulopathies and related disorders v0.4 | TBCE |
Zornitza Stark gene: TBCE was added gene: TBCE was added to Renal Tubulopathies and related disorders. Sources: Literature,Expert Review Green Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TBCE were set to 27666369 Phenotypes for gene: TBCE were set to Hypoparathyroidism-retardation-dysmorphism syndrome, OMIM #241410 |
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| Renal Tubulopathies and related disorders v0.4 | RET |
Zornitza Stark gene: RET was added gene: RET was added to Renal Tubulopathies and related disorders. Sources: Expert list,Expert Review Green Mode of inheritance for gene: RET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RET were set to 8099202; 7906866 Phenotypes for gene: RET were set to Multiple endocrine neoplasia IIB, MIM# 162300; Multiple endocrine neoplasia IIA, MIM# 171400 |
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| Renal Tubulopathies and related disorders v0.4 | CNNM2 |
Zornitza Stark gene: CNNM2 was added gene: CNNM2 was added to Renal Tubulopathies and related disorders. Sources: KidGen_Magnesium v38.1.0,Expert Review Green Mode of inheritance for gene: CNNM2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: CNNM2 were set to 35170241; 34604137 Phenotypes for gene: CNNM2 were set to Hypomagnesemia 6, renal MIM#613882; Hypomagnesemia, seizures, and mental retardation MIM#616418 |
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| Renal Tubulopathies and related disorders v0.4 | ATP1A1 |
Zornitza Stark gene: ATP1A1 was added gene: ATP1A1 was added to Renal Tubulopathies and related disorders. Sources: Literature,Expert Review Green Mode of inheritance for gene: ATP1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP1A1 were set to 30388404 Phenotypes for gene: ATP1A1 were set to Charcot-Marie-Tooth disease, axonal, type 2DD, OMIM #618036; Hypomagnesemia, seizures, and mental retardation 2, OMIM #618314 |
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