[Clinical, genetic and molecular studies on autosomal dominant polycystic kidney disease].

BACKGROUND

Two genes causing autosomal dominant polycystic kidney disease (ADPKD), PKD1 and PKD2, have been described. In the present work we study, by means of linkage analysis, the genetic heterogeneity in our population as well as the clinical differences between PKD1 and PKD2.

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 techniques used to analyze the microsatellites have been the chemiluminescence and the silver satining techniques. All the subjects underwent a complete physical examination and a sonographic scan. Clinical and molecular 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 onset of end stage renal disease (53.4 vs. 72.7 years, p < 0.00001), and earlier age at diagnosis of hypertension (34.8 vs. 49.7 years; p = 0.001) and a higher prevalence 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 PKD2) but this was not a widespread phenomenon. Our data do not support the phenomenon of genetic imprinting for this disease.

CONCLUSION

In the population of Catalonia, Spain, PKD1 accounts for 85% of families with autosomal dominant polycystic kidney disease and PKD2 accounts for the remaining 15%. PKD1 form is more severe than PKD2.