Identification of a new locus for medullary cystic disease, on chromosome 16p12

Autosomal dominant medullary cystic disease (ADMCKD) is an interstitial nep hropathy that has morphologic and clinical features similar to autosomal re cessive nephronophthisis. The typical renal dysfunction associated with ADM CKD results mainly from a defect in urinary concentration ability, although results of urinalysis are normal. Recently, a locus on chromosome 1 was as sociated with ADMCKD, in DNA from two large Cypriot families, and genetic h eterogeneity was inferred. We describe the genomewide linkage mapping of a new locus for medullary cystic disease, ADMCKD2, on chromosome 16p12 in a f our-generation Italian pedigree. The family with ADMCKD2 fulfills the typic al diagnostic criteria of ADMCKD, complicated by hyperuricemia and gouty ar thritis. Marker D16S3036 shows a maximum two-point LOD score of 3.68, and t he defined critical region spans 10.5 cM, between D16S500 and SCNN1B1-2. Ca ndidate genes included in the critical region are discussed.