AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE WITH MINIMAL CLINICAL EXPRESSION UNLINKED TO THE PKD1 LOCUS

Autosomal dominant polycystic kidney disease (ADPKD) is caused by muta tions at the PKD1 locus in most families. This locus has been assigned to the short arm of chromosome 16 by linkage analysis. It has been es timated that approximately 5% of families have a disease that does not map to this locus and most of these families have clinical features i ndistinguishable from the disease caused by PKD 1 mutations. We report a large three-generation Caucasian family from Northern Ireland with ADPKD in whom all affected individuals (age range 22-68) were normoten sive and only the two eldest had mild renal impairment. Linkage was ex cluded between the disease and both the alpha-globin gene complex and the microsatellite marker D16S283. This family confirms that phenotypi c heterogeneity exists between unlinked families and that certain non- PKD1 mutations cause mild disease expression. Many such individuals ma y therefore remain undetected and the incidence of families with ADPKD who have non-PKD1 mutations may be greater than previously estimated.