GENETIC-LINKAGE ANALYSIS, CLINICAL-FEATURES AND PROGNOSIS OF AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE IN NORTHERN-IRELAND

Fifteen families with autosomal dominant polycystic kidney disease wer e analysed for coinheritance of the disease and DNA markers flanking t he PKD1 locus. Eleven families demonstrated linkage to PKD1 markers. T wo families were unlinked to the PKD1 locus (non-PKD1) and in two fami lies the markers were uninformative. The clinical features and prognos is 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%) o f PKD1 subjects (p<0.002). Hypertension was more common in PKD1 compar ed 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. H owever, the proportion of non-PKD1 families appears to be higher than estimates for other populations. This study also confirms initial repo rts that subjects with a non-PKD1 genotype have a milder disease with a better prognosis than those with a PKD1 genotype.