DNA MICROSATELLITE ANALYSIS OF FAMILIES WITH AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE TYPE-1 AND TYPE-2 - EVALUATION OF CLINICAL HETEROGENEITY BETWEEN BOTH FORMS OF THE DISEASE

We studied 17 large families affected by adult dominant polycystic kid ney disease (ADPKD). Ultrasonographic analysis was performed on all th e family members. DNA microsatellite markers closely linked to PKD1 on 16p13.3 were analysed, and linkage of the disease to this locus was d etermined. Families showing a negative linkage value were evaluated fo r linkage to the PKD2 locus on 4q. Five of the 17 families showed nega tive Linkage for the 16p13 3 markers. In these families significant li nkage to 4q was obtained. Renal cysts developed at an earlier age in P KD1 mutation carriers, and end stage renal failure occurred at an olde r age in people affected with PKD2. Analysis of large families with AD PKD in a Spanish population indicates that this is a genetically heter ogeneous disorder, but mutations at only two loci are responsible for the development of the disease in most if not all the families. Clinic opathological differences between both forms of the disease occur, wit h subjects with ADPKD2 having a better prognosis than those with mutat ions at PKD1.