[Autosomal dominant polycystic kidney disease in Iceland - genetic study.]

Autosomal dominand polycystic kidney disease (ADPKD) is one of the most common genetic diseases in humans and accounts for 8-10% of end-stage renal failure. The disease is caused by mutations in at least three different genes. About 85% of families with ADPKS have a mutation in a gene (PKD1) on chromosome 16p, whereas 10-15% have a mutation in a gene (PKD2) on chromosom 4q. In a few families, a third gene (PKD3) of unkonown location appears to be involved. The purpose of this study was to determine the genotype of Icelandic families with ADPKD.

We isloated DNA from 229 family members and generated genotypes for polymorphic markers with conventional methods. Linkage analysis and haplotype analysis weere performed in 14 ADPKD families, employing merkers from the PKD1 and PKD2 regions.

The abnormal gene could be located in 13 families. Eleven families demonstrated linkage to the PKD2 locus. Comparison of the haplotypes of the PKD1 families indicates that nine different mutations cause ADPKD1 in Iceland, including one de novo mutation. The two ADPKD2 families each have a distinct haplotype. Thererfor, at least 11 different mutations cause ADPKD in Icelnad. In cooperation with Dutch scientists, one mutation in the PKD2 gene was defined, a 16 bp deletion of a spice site between intron 1 and exon 2.

Our results demonstrate marked genetic heterogeneity of ADPKD in the Icelandic population. As expected, most of the families have evidence for mutation in the PKD1 gene. The stage has been set for future work, which will focus on detecting mutations in the PKD genes and defining the correlation between mutations and phenotype of the disease.