Novel and recurrent mutations in the PKD1 (polycystic kidney disease) gene

A search has been conducted for disease-causing mutations in the PKD1 gene in 147 unrelated ADPKD index cases. Using the polymerase chain reaction with primer pairs located in the 3' single copy region of the gene and single-strand conformation polymorphism analysis, we detected novel aberrant bands in five individuals that were absent in 100 control samples. Sequencing revealed three nonsense mutations (Q4010X, E4024X, Q4041X), a frameshift mutation (12262 del 2 bp), and a missense mutation (G4031D). In addition, three polymorphisms were detected [12346 + 19delG, heterozygosity (0.13), I4044V (0.23), 12212-34C > A (0.07)]. The mutational mechanism for the recurrent mutation (Q4041X) is likely to be slipped mispairing of an adjacent direct imperfect repeat sequence.