Clinical and genetic characterization of an autosomal dominant nephropathy

Autosomal dominant familial nephropathies with adult onset, no macroscopic cysts, and progressive deterioration include medullary cystic disease (ADMC KD) as well as other less specific entities. We studied a kindred of Jewish ancestry in which 15 members (both male and female) have suffered from chr onic renal failure. The first evidence of renal involvement was observed be tween 18 and 38 years, It included hypertension followed by progressive ren al insufficiency. No polyuria, anemia, gout, hematuria, nor proteinuria wer e seen, An average of 4.5 years elapsed from diagnosis to endstage renal di sease. Renal pathology at early stages of the disease showed extensive tubu lointerstitial fibrosis and global glomerulosclerosis, Linkage analysis was performed at the two known loci of ADMCKD, on Chromosomes 1 and 16, Linkag e to the chromosome 16 locus was excluded. However, linkage to the chromoso me 1q21 locus of ADMCKD was established with a maximum two-point LOD score of 3.82 to D1S394, The disease interval could be narrowed to about 9 cM/7.4 Rib between D1S1156 and D1S2635, Multiple-point linkage analysis revealed a maximum LOD of 4.21, with a broad peak from markers D1S2858 and D1S2624, This report establishes linkage between a familial nephropathy characterize d by hypertension and progressive renal failure to the locus described for ADMCKD, a disease classically associated with macroscopic corticomedullary cysts, salt-losing tubulointerstitial nephropathy, and anemia. This finding broadens the clinical spectrum of ADMCKD positioned on chromosome 1q21 loc us,(C) 2001 Wiley-Liss,Inc.