Linkage analysis for the diagnosis of autosomal dominant polycystic kidney disease, and for the determination of genetic heterogeneity in Italian families

Sixty-eight individuals from six Italian families in which autosomal dominant polycystic kidney disease (ADPKD) is segregating, were typed in DNA polymorphisms linked to the PKD1 locus on chromosome 16. A total of ten probes were used: 3′ HVR, HMJ1, EKMDA, GGG1, 26–6, VK5B, 218EP6, 24.1, CR1090, and 41.1. Zmax was 4.502 at theta = 0.082 between ADPKD and 3′ HVR, and 4.382, 1.947, and 1.576 between ADPKD and GGG1, 26.6, and 218EP6, respectively, at theta = 0.0. No clear evidence of genetic heterogeneity was found. Multipoint analyses were consistent with linkage to PKD1. Twenty-nine diagnoses and 16 exclusions made by ultrasonography were confirmed by genotype determinations; in two clinically uncertain cases, DNA analysis predicted one individual as being affected and the other unaffected.