Novel mutations in the duplicated region of the polycystic kidney disease 1 (PKD1) gene provides supporting evidence for gene conversion.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common human single-gene disorders, and is the most common inherited form of cystic kidney disease. It is estimated that approximately 85% of ADPKD is due to mutations in the PKD1 gene, which is located on chromosome 16p13.3. Mutation analysis in this gene is difficult, because more than two-thirds of reiterated several times at 16p13.1. In this study, mutation screening in 90 ADPKD patients was carried out on exons in the duplicated region of the PKD1 gene (23-34), using genomic long-range PCR followed by nested PCR and single-strand conformation polymorphism (SSCP), and finally cycle sequencing. Two nonconservative missense mutations were detected in exons 25 and 31, and two conservative mutations were found in exons 24 and 29. A novel splicing mutation, which is expected to cause skipping of exon 30, was detected in one case. Moreover, six intronic variants, three silent variants, and one polymorphic variant were detected in this study. Comparison between some of these changes and published sequences from the homologous genes on 16p13.1, revealed supporting evidence for the gene conversion theory as a mechanism responsible for some of the mutations in the PKD1 gene. Factors likely to facilitate gene conversion in this region of the PKD1 gene are discussed.