Modifiers of Autosomal Dominant Polycystic Kidney Disease Severity: The Role of PKD1 Hypomorphic Alleles.

ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure in adult life. Rarely, ADPKD can be diagnosed in utero or in infancy, and the genetic mechanism underlying such severe presentation has been shown to be related to reduced gene dosage. Biallelic PKD1 variants are often identified in early onset ADPKD, with one main pathogenic variant and a modifier hypomorphic variant showing an in trans configuration. We describe two unrelated individuals with early onset cystic kidney disease and unaffected parents, where a combination of next-generation sequencing of cystic genes including PKHD1, HNF1B and PKD1 allowed the identification of biallelic PKD1 variants. Furthermore, we review the medical literature in ord

SUBMITTER: Ambrosini E 

PROVIDER: S-EPMC10298634 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature