The diversity of PKD1 alleles: implications for disease pathogenesis and genetic counseling

Abstract

Rossetti et al. identify non- and incompletely penetrant alleles of PKD1. Although such alleles are well recognized in other human mendelian disorders, they have not been associated with autosomal dominant polycystic kidney disease (ADPKD). These alleles produce atypical, mild, or severe disease depending on whether they are inherited in the heterozygous or homozygous state or in trans with another mutation, providing an intriguing potential mechanism for the considerable phenotypic variability seen in families with ADPKD.