PubMed 22034641

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Automatically associated channels: Kv2.1

Title: Mutations in multiple PKD genes may explain early and severe polycystic kidney disease.

Authors: Carsten Bergmann, Jennifer von Bothmer, Nadina Ortiz Brüchle, Andreas Venghaus, Valeska Frank, Henry Fehrenbach, Tobias Hampel, Lars Pape, Annegret Buske, Jon Jonsson, Nanette Sarioglu, Antónia Santos, Jose Carlos Ferreira, Jan U Becker, Reinhold Cremer, Julia Hoefele, Marcus R Benz, Lutz T Weber, Reinhard Buettner, Klaus Zerres

Journal, date & volume: J. Am. Soc. Nephrol., 2011 Nov , 22, 2047-56

PubMed link:

Autosomal dominant polycystic kidney disease (ADPKD) is typically a late-onset disease caused by mutations in PKD1 or PKD2, but about 2% of patients with ADPKD show an early and severe phenotype that can be clinically indistinguishable from autosomal recessive polycystic kidney disease (ARPKD). The high recurrence risk in pedigrees with early and severe PKD strongly suggests a common familial modifying background, but the mechanisms underlying the extensive phenotypic variability observed among affected family members remain unknown. Here, we describe severely affected patients with PKD who carry, in addition to their expected familial germ-line defect, additional mutations in PKD genes, including HNF-1β, which likely aggravate the phenotype. Our findings are consistent with a common pathogenesis and dosage theory for PKD and may propose a general concept for the modification of disease expression in other so-called monogenic disorders.