DNA microsatellite analysis of families with autosomal dominant polycystic kidney disease types 1 and 2: evaluation of clinical heterogeneity between both forms of the disease.

Abstract

We studied 17 large families affected by adult dominant polycystic kidney disease (ADPKD). Ultrasonographic analysis was performed on all the family members.DNA microsatellite markers closely linked to PKD1 on 16pl3 3 were analysed, and linkage of the disease to this locus was determined. Families showing a negative linkage value were evaluated for linkage to the PKD2 locus on 4q.Five of the 17 families showed negative linkage for the 16pl3.3 markers. In these families significant linkage to 4q was obtained. Renal cysts developed at an earlier age in PKD1 mutation carriers, and end stage renal failure occurred at an older age in people affected with PKD2.Analysis of large families with ADPKD in a Spanish population indicates that this is a genetically heterogeneous disorder, but mutations at only two loci are responsible for the development of the disease in most if not all the families. Clinicopathological differences between both forms of the disease occur, with subjects with ADPKD2 having a better prognosis than those with mutations at PKD1.

Genotypes of autosomal dominant polycystic kidney disease in Japanese

“…Microsatellite markers 16AC2.5, CW2, SM7 are localized within 350 kb of the PKD1 gene (Harris et al 1991;Thompson et al 1992;Viribay et al 1994). Microsatellite marker D16S521 is located distal to the PKD1 gene (Coto et al 1995). To assess linkage to PKD2, six markers, D4S231, D4S1534, D4S1542, D4S1563, D4S1544, and D4S414 (Mills et al 1992), were used.…”

A mechanistic approach to inherited polycystic kidney disease

“…Mutations in one gene, known as PKD1, account for 85%-90% of cases. Mutations in the other gene, known as PKD2, result in a similar phenotype, but the manifestations are less severe and end-stage renal disease tends to be reached later [5]. Very rare families fail to have linkage to either of these loci, suggesting a third locus.…”

Autosomal Dominant Polycystic Kidney Disease – Clinical and Genetic Aspects

“…So the share of non-PKD1 pedigrees in North England is 5% [109], in Spain 15% [110], in Italy 27% [111] and in Bulgaria 27.3% [64]. The estimate of locus heterogeneity in ADPKD is important for the choice of a systemic approach for genetic diagnostics of the disease in a given population.…”