Confirmation of a gene locus for medullary cystic kidney disease (MCKD2) on chromosome 16p12

Background. Autosomal-dominant medullary cystic kidney disease (MCKD) is an interstitial nephropathy characterized by structural renal tubular defects that result in salt wasting and a reduction in urinary concentration. The condition has clinical and morphological similarities to autosomal-recessiv e juvenile nephronophthisis. Two genes predisposing to MCKD have been local ized. MCKD1 on chromosome 1q21 was localized in two Cypriot families, and M CKD2 on chromosome 16p12 was localized in a single Italian family. We have evaluated a large Welsh MCKD family for linkage at these two loci. Methods. Clinical data and DNA samples were collected from affected family members. Polymorphic microsatellite markers spanning the critical regions o n chromosome 1 and chromosome 16 that encompass MCKD1 and MCKD2 were analyz ed. Two-point and multipoint LOD scores were calculated. Results. The family fulfilled previously published criteria for the diagnos is of MCKD. but hyperuricemia and gout were not prominent features. Twenty- one affected individuals were identified. Mean age at death or end-stage re nal disease was 47 years (37 to 60). Linkage and haplotype analysis generat ed strongly negative results at MCKD1 on chromosome 1q21 (two-point LOD sco re = -5.32). Strong evidence of linkage to MCKD2 was generated with a maxim um multi-point LOD score of 3.75. Conclusion. These results provide the first independent confirmation of a g ene predisposing to MCKD on chromosome 16p12 and indicate that mutation of this gene is not restricted to a single family or population. The absence o f hyperuricemia and gout in our family indicates that these are not obligat ory features of MCKD2 mutations.