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| Unexplained young onset end-stage renal disease v3.35 | CLCNKB | Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Sarah Leigh in 'R256 Nephrocalcinosis or nephrolithiasis' and 'R198 Renal tubulopathies' panels, the mode of inheritance for CLCNKB should be BIALLELIC, autosomal or pseudoautosomal. Although digenic CLCNKB & CLCNKA variants are associated with Bartter syndrome, type 4b, digenic (OMIM:613090), this phenotype is not relevant to this panel and the current GMS rare disease bioinformatic pipeline does not allow for interpretation of digenic events. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v3.30 | WDR72 |
Achchuthan Shanmugasundram gene: WDR72 was added gene: WDR72 was added to Unexplained young onset end-stage renal disease. Sources: Expert Review Mode of inheritance for gene: WDR72 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WDR72 were set to 30028003; 30779877; 31959358; 33033857 Phenotypes for gene: WDR72 were set to Amelogenesis imperfecta, type IIA3, OMIM:613211 Review for gene: WDR72 was set to RED Added comment: Reviews from Eleanor Williams in 'R198 Renal tubulopathies' panel: Additional families reported with distal renal tubular acidosis, along with amelogenesis imperfecta. PMID: 30779877 (Zhang et al 2019) - 6 families (1 African, 5 Turkish) identified using WES with biallelic WDR72 variants. The affected members showed generalized hypomaturation Amelogenesis imperfecta. 2 families, although unrelated, shared the same variant. 3 out of the 8 tested patients showed decreased serum pH, consistent with a diagnosis of renal tubular acidosis. PMID: 31959358 - (Jobst-Schwan et al 2020) - 2 families (Indian, Turkish) with different homozygous variants in WDR72 identified by WES. All 3 affected individuals had Distal renal tubular acidosis. 1 individual is reported to have nephrocalcinosis. PMID: 33033857 - Khandelwal et al 2021 - 4 patients, from three unrelated consanguineous families, with RTA and amelogenesis imperfecta. Genome analysis of 3 of the patients identified 3 different homozygous nonsense variants in WDR72. Ultrasound showed bilateral grade I medullary nephrocalcinosis in the 3 patients. Created: 1 Mar 2023, 9:46 p.m. | Last Modified: 1 Mar 2023, 9:46 p.m. Panel Version: 3.4 Comment on list classification: Rating this gene as amber as 2 reported families to date. Created: 12 Feb 2019, 10:38 p.m. No association with a renal phenotype in OMIM (only with Amelogenesis imperfecta) or Gene2Phenotype. PMID: 30028003 (Rungroj et al 2018) report 2 families, of Thai and Indian ethnicities, with compound heterozygous and homozygous nonsense WDR72 variations respectively. Both were affected by hereditary distal renal tubular acidosis (dRTA). 3 different variants were found in WDR72; c.1777A>G:p.R593G and c.2522T>A:p.L841Q (predicted as disease causing or damaging, found as compound heterzygotes in family 1) and c.2686C>T:p.R896X. (protein truncating, homozygous in family 2). The truncating variant has been previously reported in a Pakistani family affected by hypomaturation AI, however no other clinical phenotypes in the patients were reported (PMID: 21196691). Patients in family 1 presented with proximal muscle weakness and/or growth retardation at ages under 7 years. One member of family 1 also had nephrolithiasis and localized enamel hypoplasia. Family 2 has consanguineous parents with one affected child which presented with hypoplastic amelogenesis imperfect in addition to dRTA. She also showed nephrocalcinosis. Created: 12 Feb 2019, 10:36 p.m. | Last Modified: 1 Mar 2023, 7:39 p.m. Panel Version: 3.4 Sources: Expert Review |
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| Unexplained young onset end-stage renal disease v3.21 | TTR | Achchuthan Shanmugasundram reviewed gene: TTR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Amyloidosis, hereditary, transthyretin-related 105210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v3.21 | CNNM2 | Achchuthan Shanmugasundram reviewed gene: CNNM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: renal hypomagnesemia 6, MONDO:0013480, Hypomagnesemia, seizures, and mental retardation, MONDO:0014631, Hypomagnesemia 6, renal, OMIM:613882, Hypomagnesemia, seizures, and mental retardation, OMIM:616418; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v3.21 | ATP1A1 | Achchuthan Shanmugasundram reviewed gene: ATP1A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypomagnesemia, seizures, and mental retardation 2 618314, Charcot-Marie-Tooth disease, axonal, type 2DD, 618036; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v3.17 | TTR |
Achchuthan Shanmugasundram gene: TTR was added gene: TTR was added to Unexplained young onset end-stage renal disease. Sources: Expert Review Amber,NHS GMS Mode of inheritance for gene: TTR was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: TTR were set to Amyloidosis, hereditary, transthyretin-related 105210 |
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| Unexplained young onset end-stage renal disease v3.17 | CNNM2 |
Achchuthan Shanmugasundram gene: CNNM2 was added gene: CNNM2 was added to Unexplained young onset end-stage renal disease. Sources: Expert Review Amber,NHS GMS 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 Phenotypes for gene: CNNM2 were set to Hypomagnesemia, seizures, and mental retardation, OMIM:616418; renal hypomagnesemia 6, MONDO:0013480; Hypomagnesemia, seizures, and mental retardation, MONDO:0014631; Hypomagnesemia 6, renal, OMIM:613882 Mode of pathogenicity for gene: CNNM2 was set to Other |
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| Unexplained young onset end-stage renal disease v3.17 | ATP1A1 |
Achchuthan Shanmugasundram gene: ATP1A1 was added gene: ATP1A1 was added to Unexplained young onset end-stage renal disease. Sources: Expert Review Amber,NHS GMS Mode of inheritance for gene: ATP1A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: ATP1A1 were set to Hypomagnesemia, seizures, and mental retardation 2 618314; Charcot-Marie-Tooth disease, axonal, type 2DD, 618036 |
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| Unexplained young onset end-stage renal disease v3.13 | CD151 | Achchuthan Shanmugasundram Phenotypes for gene: CD151 were changed from Nephropathy with pretibial epidermolysis bullosa and deafness 609057 to Epidermolysis bullosa simplex 7, with nephropathy and deafness, OMIM:609057 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v3.9 | RET | Sarah Leigh Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v3.9 | RET | Achchuthan Shanmugasundram Tag Q2_23_MOI was removed from gene: RET. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v3.9 | RET | Achchuthan Shanmugasundram Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v3.9 | RET | Achchuthan Shanmugasundram commented on gene: RET: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v3.8 | RET | Sarah Leigh commented on gene: RET: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v3.7 | RET | Sarah Leigh edited their review of gene: RET: Added comment: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v3.6 | RET | Achchuthan Shanmugasundram changed review comment from: Comment on MOI: Renal agenesis (MIM #191830) is caused by biallelic variants in ITGA8 rather than by biallelic RET variants as suggested in the reviews below. OMIM clearly associates renal agenesis with ITGA8. Biallelic variants in RET has only been associated with renal agenesis in Gene2Phenotype with 'limited' rating, which requires clinical review/. This association was based on OMIM entry and do not have any associated publications. In addition, all other renal related conditions are monoallelic. Hence the MOI should be changed to monoallelic.; to: Comment on MOI: Renal agenesis (MIM #191830) is caused by biallelic variants in ITGA8 rather than by biallelic RET variants as suggested in the reviews below. OMIM clearly associates renal agenesis with ITGA8. Biallelic variants in RET has only been associated with renal agenesis in Gene2Phenotype with 'limited' rating, which requires clinical review. This association was based on OMIM entry and do not have any associated publications. In addition, all other renal related conditions are monoallelic. Hence the MOI should be changed to monoallelic. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v3.6 | RET |
Achchuthan Shanmugasundram Source NHS GMS was added to RET. Mode of inheritance for gene RET was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
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| Unexplained young onset end-stage renal disease v3.1 | RET | Achchuthan Shanmugasundram Tag Q2_23_MOI tag was added to gene: RET. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v3.1 | RET | Achchuthan Shanmugasundram reviewed gene: RET: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v1.6 | CD151 | Eleanor Williams Phenotypes for gene: CD151 were changed from to Nephropathy with pretibial epidermolysis bullosa and deafness 609057 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v1.3 | CD151 |
Eleanor Williams edited their review of gene: CD151: Added comment: Associated with Nephropathy with pretibial epidermolysis bullosa and deafness #609057 in OMIM. The 3 patients from 2 families described in PMID: 15265795 - Karamatic Crew et al 2004 all had end-stage kidney disease and homozygous insertion in the CD151 gene. Although they are described as unrelated both families are of Indian Jewish origin. The ages of the patients are not reported. Another case is described in PMID: 29138120 - Vahidnezhad et al 2018 where the patient had history of nephropathy with proteinuria. PMID: 17015618 - Sachs et al 2006 - report the generation of Cd151-null mice that recapitulate the renal pathology of human patients, i.e., with age they develop massive proteinuria; Changed publications: 15265795, 29138120, 17015618; Changed phenotypes: Nephropathy with pretibial epidermolysis bullosa and deafness 609057; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal |
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| Unexplained young onset end-stage renal disease v1.1 | BNC2 | Eleanor Williams Phenotypes for gene: BNC2 were changed from Posterior urethral valves; PUV; Congenital lower urinary-tract obstruction to Posterior urethral valves; PUV; Congenital lower urinary-tract obstruction; Lower urinary tract obstruction, congenital, 618612 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.49 | RET | Eleanor Williams commented on gene: RET: Note on MOI - keeping BOTH mono and biallelic because Gene2Phenotype has Renal agenesis as biallalic. All other renal related conditions are monoallelic. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.14 | BNC2 | Louise Daugherty Phenotypes for gene: BNC2 were changed from Posterior urethral valves; PUV to Posterior urethral valves; PUV; Congenital lower urinary-tract obstruction | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.13 | BNC2 | Louise Daugherty edited their review of gene: BNC2: Added comment: New publication PMID: 31051115 Kolvenbach CM et al., (2019) supports the rating of this gene from Amber to Green. Though exome sequencing in a family with four affected individuals with anatomical blockage of the urethra identified a rare nonsense variant (c.2557C>T [p.Arg853∗]) in BNC2, encoding basonuclin 2, tracking with LUTO over three generations. Re-sequencing BNC2 in 697 individuals with LUTO revealed three further independent missense variants in three unrelated families. In human and mouse embryogenesis, basonuclin 2 was detected in lower urinary-tract rudiments. In zebrafish embryos, bnc2 was expressed in the pronephric duct and cloaca, analogs of the mammalian lower urinary tract. Experimental knockdown of Bnc2 in zebrafish caused pronephric-outlet obstruction and cloacal dilatation, phenocopying human congenital LUTO. Collectively, these results support the conclusion that variants in BNC2 are strongly implicated in LUTO etiology as a result of anatomical blockage.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.2 | RET | Eleanor Williams reviewed gene: RET: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.1 | ISCA-37405-Loss |
Eleanor Williams Region: ISCA-37405-Loss was added Region: ISCA-37405-Loss was added to Unexplained paediatric onset end-stage renal disease. Sources: Expert Review Green Mode of inheritance for Region: ISCA-37405-Loss was set to BIALLELIC, autosomal or pseudoautosomal Publications for Region: ISCA-37405-Loss were set to 9856524; 8852662; 15138899 Phenotypes for Region: ISCA-37405-Loss were set to 609583; 266900; juvenile nephronophthisis 1: including growth retardation. Joubert syndrome: multisystem disease characterized by cerebellar vermis hypoplasia with prominent superior cerebellar peduncles (resulting in the 'molar tooth sign,' or MTS, on axial MRI), mental retardation, hypotonia, irregular breathing pattern, and eye movement abnormalities |
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| Unexplained young onset end-stage renal disease v0.1 | ISCA-37401-Loss |
Eleanor Williams Region: ISCA-37401-Loss was added Region: ISCA-37401-Loss was added to Unexplained paediatric onset end-stage renal disease. Sources: Expert Review Green Mode of inheritance for Region: ISCA-37401-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for Region: ISCA-37401-Loss were set to 194072; Wilms tumor, aniridia, genitourinary anomalies and mental retardation syndrome |
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| Unexplained young onset end-stage renal disease v0.1 | SOX17 |
Eleanor Williams gene: SOX17 was added gene: SOX17 was added to Unexplained paediatric onset end-stage renal disease. Sources: Expert Review Red Mode of inheritance for gene: SOX17 was set to Unknown Phenotypes for gene: SOX17 were set to Vesicoureteral reflux 3, 613674 |
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| Unexplained young onset end-stage renal disease v0.1 | ROBO2 |
Eleanor Williams gene: ROBO2 was added gene: ROBO2 was added to Unexplained paediatric onset end-stage renal disease. Sources: Expert Review Red Mode of inheritance for gene: ROBO2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: ROBO2 were set to Vesicoureteral Reflux; Vesicoureteral reflux 2, 610878 |
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| Unexplained young onset end-stage renal disease v0.1 | BNC2 |
Eleanor Williams gene: BNC2 was added gene: BNC2 was added to Unexplained paediatric onset end-stage renal disease. Sources: Other,Expert Review Amber Mode of inheritance for gene: BNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: BNC2 were set to Posterior urethral valves; PUV Mode of pathogenicity for gene: BNC2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments |
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| Unexplained young onset end-stage renal disease v0.1 | RET |
Eleanor Williams gene: RET was added gene: RET was added to Unexplained paediatric onset end-stage renal disease. Sources: Expert Review Green Mode of inheritance for gene: RET was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: RET were set to Multiple endocrine neoplasia IIB, 162300; Central hypoventilation syndrome, congenital, 209880; Multiple endocrine neoplasia IIA, 171400; Renal agenesis, 191830; {Hirschsprung disease, susceptibility to, 1}, 142623; Pheochromocytoma, 171300; Renal Adysplasia; Medullary thyroid carcinoma, 155240 |
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| Unexplained young onset end-stage renal disease v0.1 | DSTYK |
Eleanor Williams gene: DSTYK was added gene: DSTYK was added to Unexplained paediatric onset end-stage renal disease. Sources: Expert Review Green Mode of inheritance for gene: DSTYK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: DSTYK were set to Renal hypodysplasia; {Congenital anomalies of kidney and urinary tract, susceptibility to}; CONGENITAL ANOMALIES OF KIDNEY AND URINARY TRACT, CAKUT1; ureteropelvic junction obstruction; {Congenital anomalies of kidney and urinary tract, susceptibility to}, 610805; vesicoureteric reflux |
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| Unexplained young onset end-stage renal disease v0.1 | COL4A1 |
Eleanor Williams gene: COL4A1 was added gene: COL4A1 was added to Unexplained paediatric onset end-stage renal disease. Sources: Expert Review Green Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: COL4A1 were set to 20818663; 18160688 Phenotypes for gene: COL4A1 were set to raised creatinine kinase; tortuous retinal vessels; intracranial anuerysms; Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps 611773; Exophytic renal cysts; haematuria |
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