Four novel mutations of the PKD2 gene in Czech families with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disease caused by mutations in at least three different loci. Mutations in the PKD2 gene are responsible for approximately 15% of the cases of the disease. We have screened 14 Czech families for mutation in the PKD2 gene. Clear evidence against linkage to the PKD1 gene was established by CA-repeat markers in five families. The disease could be linked to both genes according to linkage analysis in nine families but we have chosen these families because of the mild clinical course. An affected member from each family was analyzed by heteroduplex analysis (HA) and single strand conformation polymorphism (SSCP) for all 15 coding regions. Samples exhibiting shifted bands on HA or SSCP gels were sequenced. We detected five mutations (four new, and one which was previously described) and two polymorphisms. The four new mutations include one insertion, one deletion, one substitution (leading to premature translation stop), one amino acid substitution. Our results confirm that different point or small changes distributed throughout the PKD2 gene without clustering are responsible for the disease.