Disquisition of Exome Sequencing of Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Abstract

The Key Points This study's target demonstrates significant genetic and phenotypic variation in ADPKD.

Importance The majority of research on the genetics of autosomal dominant polycystic kidney disease (ADPKD) has focused on PKD1 and PKD2 in kidney specialty cohorts. These may result in inaccurate population prevalence and phenotypic expression estimates of ADPKD-associated gene variants.

Objective In a large, unselected cohort, to ascertain the prevalence of ADPKD and the roles played by PKD1, PKD2, and other cystic kidney disease-related genes. Exposures Loss-of-function (LOF) variants in PKD1, PKD2, and other genes associated with cystic kidney disease (ie, ALG8, ALG9, DNAJB11, GANAB, HNF1B, IFT140, SEC61B, PKHD1, PRKCSH, SEC63); likely pathogenic missense variants in PKD1 and PKD2.

Main Outcomes and Measures phenotype-first analysis: presence of a rare variant in PKD1, PKD2, or other genes associated with cystic kidney disease; genotype-first analysis: ADPKD diagnosis code (Q61.2, Q61.3, 753.13, 753.12).