Heterozygous loss of function variants in IFT140 are associated with polycystic kidney disease.
IFT140
genetic testing
polycystic kidney disease
variant
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
13 Aug 2024
13 Aug 2024
Historique:
revised:
13
07
2024
received:
21
12
2023
accepted:
29
07
2024
medline:
13
8
2024
pubmed:
13
8
2024
entrez:
13
8
2024
Statut:
aheadofprint
Résumé
Autosomal dominant polycystic kidney disease (ADPKD) affects 1 in 1000 adults. Most cases result from causative PKD1 or PKD2 variants. HNF1B, GANAB and ALG9 variants are also associated with ADPKD. Recent evidence indicates that monoallelic loss-of-function (LoF) IFT140 variants are a cause for non-syndromic ADPKD. We describe 368 patients with IFT140 LoF variants and a spectrum of phenotypic findings that support the association of IFT140 with PKD. We reviewed patients with an unknown cause for their cystic disease and those with heterozygous LoF IFT140 variants classified as pathogenic or likely pathogenic from a cohort that received genetic testing using a panel of 385 renal disease-associated genes. IFT140 LoF variants were significantly enriched in patients with cystic disease when compared with those without cystic disease. A cystic phenotype was reported in 223 of the 368 (60.6%) individuals harboring an IFT140 LoF variant, 98% of which had no other identified cause for their cystic disease. Of 122 unique LoF IFT140 variants identified, 56 (46%) were frameshift, 38 (31%) nonsense, 22 (18%) splice site and 6 (5%) exon-level deletions. Only six IFT140 individuals were reported with end-stage kidney disease, consistent with observed milder clinical presentations in IFT140-related PKD. This study offers further evidence for the involvement of LoF IFT140 variants in PKD, particularly when no additional molecular etiology has been identified.
Identifiants
pubmed: 39136524
doi: 10.1002/ajmg.a.63841
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e63841Subventions
Organisme : Natera Inc
Informations de copyright
© 2024 Natera Inc. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
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