LINKAGE, CLINICAL-FEATURES, AND PROGNOSIS OF AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE TYPE-1 AND TYPE-2

Linkage analysis was performed on 49 Catalan families with autosomal d ominant polycystic kidney disease obtained via the Nephrology Departme nt and related nephrology centers. A total of 336 subjects, 267 at ris k for the disease, were investigated using three microsatellites linke d to polycystic kidney disease Type 1 (PKD 1) and three microsatellite s linked to PKD2. All of the subjects underwent physical and sonograph ic examination. The results demonstrate locus heterogeneity, with 0.85 as the maximum likelihood for the proportion of families linked to PK D 1. All of the remaining families were found to be linked to PKD2. An alysis of clinical data in the PKD1 group (N = 146) versus the PKD2 gr oup (N = 20) showed a milder form of the disease in the latter, with a later age at diagnosis (27.4 versus 41.4 yr, P = 0.0002), later age o f onset of ESRD (53.4 versus 72.7 yr, P < 0.0001), later age of diagno sis of hypertension (34.8 versus 49.7 yr, P = 0.001) and lower prevale nce of hypertension at younger ages, Sonographic findings did not diff er significantly between both groups. Although anticipation was observ ed in both groups, it did not affect the majority of families. No sign s of imprinting were found in this study, and the only gender effect w as an earlier age of onset of ESRD in men than in women (49.5 versus 5 3.1 yr in PKD 1, P < 0.01 and 70.57 versus 73.6 yr in PKD2, P = 0.1), Molecular analysis of autosomal-dominant polycystic kidney disease all ows presymptomatic diagnosis in individuals younger than age 30, and h elps in establishing prognosis.