CLINICAL, GENETIC AND MOLECULAR STUDIES O N AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE

BACKGROUND: TWO genes causing autosomal dominant polycystic kidney dis ease (ADPKD), PKD1 and PKD2, have been described. In the present work we study, by means of linkage analysis, the genetic heterogeneity in o ur population as well as the clinical differences between PKD1 and PKD 2. SUBJECTS AND METHODS: 316 subjects belonging to 49 unrelated ADPKD families have been studied by means of 3 microsatellites for PKD1 and 3 for PKD2 to differentiate if they have ADPKD type 1 or 2. The techni ques used to analyze the microsatellites have been the chemiluminescen ce and the silver satining techniques. All the subjects underwent a co mplete physical examination and a sonographic scan. Clinical and molec ular results have been correlated. RESULTS: Genetic heterogeneity has been proved, with 85% of families linked to PKD1 and 15% to PKD2, The disease is more severe in PKD1, with an earlier age at diagnosis (27.4 vs. 41.4 years; p = 0.0002), a younger age at the oset of end stage r enal disease (53.4 vs 72.7 years, p < 0.0001), an earlier age at diagn osis of hypertension (34.8 vs. 49.7 yeats; p = 0.001) and a higher pre valence of hypertension for all groups of age. In both forms of ADPKD there were families showing anticipation (8/44 for PKD1 and 2/5 for PK D2) but this was not a widespread phenomenon. Our data do not support the phenomenon of genetic imprinting for this disease. CONCLUSIONS: In the population of Catalonia, Spain, PKD1 accounts for 85% of families with autosomal dominant polycystic kidney disease and PKD2 accounts f or the remaining 15%. PKD1 form is more severe than PKD2.