Genetic linkage analysis, clinical features and prognosis of autosomal dominant polycystic kidney disease in Northern Ireland.

Fifteen families with autosomal dominant polycystic kidney disease were analysed for coinheritance of the disease and DNA markers flanking the PKD1 locus. Eleven families demonstrated linkage to PKD1 markers. Two families were unlinked to the PKD1 locus (non-PKD1) and in two families the markers were uninformative. The clinical features and prognosis of 49 subjects with a PKD1 genotype were compared with 17 non-PKD1 subjects. The age at diagnosis in non-PKD1 subjects (37 +/- 11 years) was significantly later than PKD1 subjects (25 +/- 13 years, p < 0.001). Only two (12%) non-PKD1 subjects presented initially with clinical features of autosomal polycystic kidney disease compared to 27 (55%) of PKD1 subjects (p < 0.002). Hypertension was more common in PKD1 compared to non-PKD1 subjects (29% vs. 12%), as was stage renal failure (25% vs. 6%). Seventy-five percent of non-PKD1 subjects had not developed end-stage renal failure by the age of 54 years compared to only 35% of PKD1 subjects. Most families with autosomal polycystic kidney disease in this population have disease due to mutations at the PKD1 locus. However, the proportion of non-PKD1 families appears to be higher than estimates for other populations. This study also confirms initial reports that subjects with a non-PKD1 genotype have a milder disease with a better prognosis than those with a PKD1 genotype.