2011/10/28 by Carsten Bergmann, Jennifer von Bothmer, Nadina Ortiz Brüchle +17 · 1 citation
Biochemistry, Genetics and Molecular Biology · #Genetic and Kidney Cyst Diseases #Renal and related cancers #Genetic Syndromes and Imprinting
paper · pdf · doi:10.1681/asn.2010101080
openalex publication_date 2011/10/28 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
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.