Autosomal Recessive Polycystic Kidney: Genetics

Autosomal recessive polycystic kidney disease (ARPKD) - Genetics: ARPKD is transmitted in a recessive fashion. The parents are usually unaffected. The siblings have 1 in 4 chance of being affected. Almost 80% of cases are caused by mutations in polycystic kidney and hepatic disease gene 1 (PKHD1) on chromosome 6p12. More than 300 PKHD1 mutations have been reported. Truncating mutations result in severe disease which is often fatal in the perinatal or neonatal period. Patients with missense mutations have milder disease and they usually survive into adolescence and beyond. Most patients are compound heterozygotes. A small subset of ARPKD patients carry mutations in DAZ interacting zinc finger protein 1-like (DZIP1L which encodes DZIP1L protein in the primary cilium. It produces a milder version of the disease with no perinatal/neonatal mortality.

About this image: ARPKD genes, transcripts, and proteins: (A) PKHD1 and DZIP1L genes and transcripts. (B) structure of fibrocystin/polyductin (FPC) and DAZ-interacting protein 1-like protein (DZIP1L). Proteins are not to scale. Image Credit: Cordido A, Vizoso-Gonzalez M, Garcia-Gonzalez M. Molecular Pathophysiology of Autosomal Recessive Polycystic Kidney Disease. Int. J. Mol. Sci. 2021, 22(12), 6523; https://doi.org/10.3390/ijms22126523; used under Creative Commons Attribution (CC BY) license.