Cystic kidney disease
Gene: IFT140
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 30 Jan 2023, 4:25 p.m. | Last Modified: 30 Jan 2023, 4:25 p.m.
Panel Version: 3.4
As previous reviewers, now strong evidence
PMID 34890546: Monoallelic variants described in 12 unrelated families with mild PKD associated with mild PKD with large cysts, limited kidney insufficiency, and few liver cysts.Created: 13 Jun 2022, 8:49 a.m. | Last Modified: 13 Jun 2022, 8:49 a.m.
Panel Version: 2.45
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes
cystic kidney disease; cystic liver disease
Publications
Comment on list classification: Promoting from grey to amber with a recommendation for GREEN rating following GMS review.Created: 21 May 2022, 10:28 p.m. | Last Modified: 21 May 2022, 10:28 p.m.
Panel Version: 2.45
Comment on mode of inheritance: As reviewer notes there are several biallelic cases reported with a renal phenotype (e.g. PMID: 23418020 - 3 patients with renal cysts and biallelic IFT140 variants, PMID: 27874174 - 1 patient with renal cysts and biallelic IFT140 variants) aswell as the monallelic variants reported in PMID:34890546Created: 21 May 2022, 10:25 p.m. | Last Modified: 21 May 2022, 10:25 p.m.
Panel Version: 2.42
PMID 34890546: Monoallelic variants described in 12 unrelated families with mild PKD associated with mild PKD with large cysts, limited kidney insufficiency, and few liver cysts.
Bilallelic variants associated with Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920, where renal cysts are a feature, with early progressive renal disease.
Therefore both MOIs relevant to this panel.Created: 3 Feb 2022, 9:02 a.m. | Last Modified: 3 Feb 2022, 9:02 a.m.
Panel Version: 2.31
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Cystic Kidney Disease, MONDO# 0002473, IFT140-related, dominant
Publications
This publication provides strong evidence that variants in this gene are a significant cause of polycystic kidney disease. Plausible mutations are identified in more than 3 unrelated families.Created: 12 Jan 2022, 11:27 a.m. | Last Modified: 12 Jan 2022, 11:27 a.m.
Panel Version: 2.31
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Autosomal dominant polycystic kidney disease
Publications
Very strong evidence of association of truncating IFT140 mutations and cystic kidney disease in cited paper, which includes 12 multiplex families and 26 singletons. In addition, hypothesis-free region-based variance testing (SKAT-O) independently identifying truncating variants in this gene in 100,000 Genomes Project (p=3.5e-17) and UK BioBank (p=4.5e-15) participants with cystic kidney disease (see https://genebass.org/gene/undefined/phenotype/icd_first_occurrence-132532-both_sexes--?resultIndex=gene-manhattan&resultLayout=full for UKBB analysis).
Sources: Literature, ResearchCreated: 11 Jan 2022, 1:06 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Cystic kidney disease; chronic kidney disease
Publications
Tag Q2_22_rating was removed from gene: IFT140. Tag Q2_22_NHS_review was removed from gene: IFT140.
Source Expert Review Green was added to IFT140. Source NHS GMS was added to IFT140. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q2_22_NHS_review tag was added to gene: IFT140.
Tag Q2_22_rating tag was added to gene: IFT140.
Gene: ift140 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: IFT140 were changed from Cystic kidney disease; chronic kidney disease to Short-rib thoracic dysplasia 9 with or without polydactyly, OMIM:266920; short-rib thoracic dysplasia 9 with or without polydactyly, MONDO:0009964; cystic kidney disease, MONDO:0002473
Publications for gene: IFT140 were set to 34890546
Mode of inheritance for gene: IFT140 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
gene: IFT140 was added gene: IFT140 was added to Cystic kidney disease. Sources: Literature,Research Mode of inheritance for gene: IFT140 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IFT140 were set to 34890546 Phenotypes for gene: IFT140 were set to Cystic kidney disease; chronic kidney disease Penetrance for gene: IFT140 were set to unknown Review for gene: IFT140 was set to GREEN