NOVEL STOP AND FRAMESHIFTING MUTATIONS IN THE AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE-2 (PKD2) GENE

Autosomal dominant polycystic kidney disease (ADPKD) is one of the mos t frequent inherited disorders The majority of cases are due to mutati on of the PKD1 gene, on 16p13.3, while in most of the remainder the di sease maps to the PKD2 locus, at chromosome 4q21-q23. Recently, the PK D2 gene has been positionally cloned and three nonsense mutations with in the coding sequence of the gene identified. Here we report a system atic mutation screening of all 15 exons of the PKD2 gene in chromosome 4-linked ADPKD families, using heteroduplex and SSCP analyses. We hav e identified and characterized seven novel mutations, with a detection rate of approximately 90% in the population studied. All of the mutat ions result in the premature stop of translation: four nonsense change s and three deletions. The deletions are all frameshifting, of four T nucleotides in one case and one G nucleotide in the other two. All mut ations are unique and are distributed throughout the gene without evid ence of clustering. Comparison of specific mutations with the clinical profile in ADPKD2 families shows no clear correlation.