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| Tubulointerstitial kidney disease v1.23 | GATM | Arina Puzriakova Phenotypes for gene: GATM were changed from Renal fanconi syndrome and kidney failure to Fanconi renotubular syndrome 1, OMIM:134600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tubulointerstitial kidney disease v1.21 | TTC21B | Eleanor Williams Added comment: Comment on mode of inheritance: Leaving the mode of inheritance as Both mono and biallelic for now. It does appear that monoallelic variants are potential genetic modifiers and are found in combination with variants in other renal disease associated genes (see PMID: 26940125, PMID: 21258341) so seeking GMS review as to the best mode of inheritance. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tubulointerstitial kidney disease v1.20 | TTC21B |
Eleanor Williams edited their review of gene: TTC21B: Added comment: Looking at the mode of inheritance for this gene. It is reported as both AD and AR in OMIM for Nephronophthisis 12, OMIM:613820. There are many biallelic cases reported e.g. PMID: 21258341 - Davis et al 2011 - report 5 families with isolated nephronophthisis (NPHP). Patients in 3 families had compound heterozygous variants (P209L/C552X, c.2758-2A>G/P209L, W150R/c.3264-3C>G) in TTC21B and 2 families with a milder phenotype were homozygous for the P209L variant. They observed the same haplotype at coding regions spanning the locus in all P209L homozygotes. In all 5 families individuals heterozygous for the variants were unaffected. They also report one case with compound het variants (R411X/L795P) with a syndromic Jeune Asphyxiating Thoracic Dystrophy phenotype. PMID: 26940125 - Bullich et al 2017 - TTC21B variants and nephrotic proteinuria with FSGS and tubulointerstitial lesions were identified in 2 families with homozygous (p.P209L) variants (both families from Morocco, high blood pressure noted in individuals from each), and in 1 family with compound het variants (p.P209L and p.H426D)(family from Spain). PMID:34957165 - Gambino et al 2021 - patient from a North African family with severe hypertension and chronic kidney disease at age 20. Several cases of hypertension, myopia, and severe kidney disease were reported in the extended family. A homozygous p.P209L variant was identified in TTC21B. PMID:34805047 - Bezdíčka et al 2021 - 2.5 yo patient presenting with brachydactyly, nephrotic-range proteinuria, and renal tubular acidosis, and a kidney biopsy revealed focal segmental glomerulosclerosis. She was hypertensive on admission. Compound het variants in TTC21B were identified p.Pro209Leu and p.Cys14Arg. The mother was a healthy carrier of the c.626C>T, p.Pro209Leu heterozygous variant. PMID:35289079 - Olinger et al 2022 - 2 siblings with extreme early-onset HTN, proteinuria, and progressive CKD leading to kidney failure. Compound het variants in TTC21B were identified (p.(Gln834Ter) and p.(Pro209Leu)). However, there are also reports of heterozygous variants in TTC21B in patients with kidney disease but it is thought that these may be modifier variants PMID: 26940125 - Bullich et al 2017 - rare heterozygous variants in TTC21B were found in 5 patients, 4 with glomerular disease and 1 with cystic disease, but in addition to other likely pathogenic variants in other renal disease related genes (PKD1 , COL4A3, COL4A5 and NPHS2) suggesting a modifier role of TTC21B alleles. 2 patients presented a more severe phenotype than expected. A similar frequency for the total set of rare TTC21B variants predicted to be pathogenic was found between renal patients and controls PMID: 21258341 - Davis et al 2011 - found an enrichment of pathogenic TTC21B alleles in ciliopathy patients (∼5%) and suggest that TTC21B might be a common contributor to the total mutational load in ciliopathies.; Changed publications to: 21258341, 26940125, 34957165, 34805047, 35289079 |
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| Tubulointerstitial kidney disease v1.16 | DNAJB11 | Eleanor Williams commented on gene: DNAJB11: The rating of this gene has been updated following NHS Genomic Medicine Service approval. The reviewers note a patient with likely pathogenic frameshift who had a later presentation of renal cysts on background of interstitial disease. 19 variants associated with DNAJB11 or AD PKD on HGMD. Recent collaborative paper by Huynh et al. (2020) reports a total of 77 patients (27 pedigrees) that have been described in the literature. The majority of these patients present with polycystic kidneys. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tubulointerstitial kidney disease v1.4 | DNAJB11 |
Eleanor Williams commented on gene: DNAJB11: Associated with Polycystic kidney disease 6 with or without polycystic liver disease #618061 (AD) in OMIM. PMID: 29706351 - Cornec-Le Gall et al 2018 - Initially identified DNAJB11 variants by WES in two families presenting with Autosomal-dominant polycystic kidney disease (ADPKD)-like features. In family 1 a missense variant (p.Pro54Arg) was found in two family members presenting with non-enlarged polycystic kidneys. In family 2 a frameshifting change (c.166_167insTT) was found; they presented with small renal and liver cysts. Five additional multigenerational families carrying DNAJB11 mutations were identified by targeted analysis. From analysis of the phenotype and functional studies from DNAJB11-null cells they conclude that DNAJB11-associated disease is a phenotypic hybrid of ADPKD and ADTKD, characterized by normal-sized cystic kidneys and progressive interstitial fibrosis resulting in late-onset ESRD. PMID: 29777155 - Allison 2018 - research highlight about the Cornec-Le Gall et al 2018 paper. |
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| Tubulointerstitial kidney disease v1.0 | SEC61A1 | Zornitza Stark reviewed gene: SEC61A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30586318; Phenotypes: Familial juvenile Hyperuricemic nephropathy-4 MIM 617056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tubulointerstitial kidney disease v1.0 | DNAJB11 | Zornitza Stark reviewed gene: DNAJB11: Rating: GREEN; Mode of pathogenicity: None; Publications: 29706351; Phenotypes: Tubulointerstitial disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tubulointerstitial kidney disease v0.8 | MT-TF |
Daniel Gale gene: MT-TF was added gene: MT-TF was added to Tubulointerstitial kidney disease. Sources: Literature Mode of inheritance for gene gene: MT-TF was set to MITOCHONDRIAL Publications for gene: MT-TF were set to PMID: 28267784; 11231339; 20142618; 23135609 Phenotypes for gene: MT-TF were set to Tubulointerstitial kidney disease; tubulointerstitial nephritis; renal insufficiency; renal failure Penetrance for gene: MT-TF were set to Complete Review for gene: MT-TF was set to GREEN gene: MT-TF was marked as current diagnostic Added comment: Sources: Literature |
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| Tubulointerstitial kidney disease v0.8 | ZNF423 | Eleanor Williams Added comment: Comment on list classification: Changing rating to Amber after discussion of 3 cases in NHS GMS renal specialist group call on 2019-02-04 - one case NPHP, one Joubert with PKD, one PKD/NPHP. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tubulointerstitial kidney disease v0.7 | REN | Eleanor Williams Added comment: Comment on mode of inheritance: Updated MOI to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal" after discussion in meeting with NHS GMS renal specialist group | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tubulointerstitial kidney disease v0.7 | REN | Eleanor Williams Mode of inheritance for gene: REN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tubulointerstitial kidney disease v0.4 | MUC1 | Eleanor Williams commented on gene: MUC1: PMID: 23396133 (Kirby et al 2013) describe 6 families with an insertion of a single C in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (~1.5-5 kb), GC-rich (>80%), coding VNTR in the mucin 1 gene. The insertion results in a frameshift which is predicted to produce a mutant protein that contains many copies of a novel repeat sequence but which lacks, owing to a novel stop codon shortly beyond the VNTR terminus, the downstream SEA self-cleavage module and both transmembrane and intracellular domains characteristic of the normal MUC1 precursor protein. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tubulointerstitial kidney disease v0.3 | GATM |
Eleanor Williams edited their review of gene: GATM: Added comment: PMID: 29654216 (Reichold et al 2018) reports 5 families with with a novel form of autosomal dominant kidney disease characterized by renal tubular Fanconi syndrome early in life followed by progression to renal glomerular failure in mid-adulthood. All patients show monoallelic mutations in the gene GATM. 4 heterozygous missense mutations of evolutionary conserved amino acid residues in GATM were found (c.958C>T, p.P320S; c.1006A>G, p.T336A; c.1007C>T, p.T336I; c.1022C>T, p.P341L). In each family, one variant segregated with the disorder and was fully penetrant. In silico analysis showed that the particular GATM mutations create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells.; Changed publications: 29654216 |
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| Tubulointerstitial kidney disease v0.3 | GATM | Eleanor Williams reviewed gene: GATM: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments; Publications: ; Phenotypes: Renal fanconi syndrome and kidney failure; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tubulointerstitial kidney disease v0.3 | NPHP3 | Eleanor Williams reviewed gene: NPHP3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Nephronopthisis 3 MIM 604387, Meckel syndrome 7, MIM 267010, Renal-hepatic-pancreatic dysplasia 1, MIM 208540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tubulointerstitial kidney disease v0.3 | REN | Eleanor Williams reviewed gene: REN: Rating: GREEN; Mode of pathogenicity: ; Publications: Zivna et al 2009 PMID: 19664745, Gribouval et al 2005 PMID: 16116425; Phenotypes: Familial juvenile Hyperuricemic nephropathy-2 MIM 613092, Renal tubular dysgenesis MIM 267430; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tubulointerstitial kidney disease v0.3 | HNF1B | Eleanor Williams reviewed gene: HNF1B: Rating: GREEN; Mode of pathogenicity: ; Publications: Edghill et al 2006 PMID: 15930087; Phenotypes: Renal cysts and diabetes syndrome MIM 137920, NIDDM MIM 125853; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tubulointerstitial kidney disease v0.2 | GATM |
Eleanor Williams gene: GATM was added gene: GATM was added to Tubulointerstitial kidney disease. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: GATM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: GATM were set to Renal fanconi syndrome and kidney failure Mode of pathogenicity for gene: GATM 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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| Tubulointerstitial kidney disease v0.2 | NPHP3 |
Eleanor Williams gene: NPHP3 was added gene: NPHP3 was added to Tubulointerstitial kidney disease. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: NPHP3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NPHP3 were set to Renal-hepatic-pancreatic dysplasia 1, MIM 208540; Meckel syndrome 7, MIM 267010; Nephronopthisis 3 MIM 604387 |
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| Tubulointerstitial kidney disease v0.2 | REN |
Eleanor Williams gene: REN was added gene: REN was added to Tubulointerstitial kidney disease. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: REN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: REN were set to 16116425; 19664745 Phenotypes for gene: REN were set to Renal tubular dysgenesis MIM 267430; Familial juvenile Hyperuricemic nephropathy-2 MIM 613092 |
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| Tubulointerstitial kidney disease v0.2 | HNF1B |
Eleanor Williams gene: HNF1B was added gene: HNF1B was added to Tubulointerstitial kidney disease. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: HNF1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HNF1B were set to 15930087 Phenotypes for gene: HNF1B were set to Renal cysts and diabetes syndrome MIM 137920; NIDDM MIM 125853 |
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