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 (ADMCKD) 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 chronic renal failure. The first evidence of renal involvement was observed between 18 and 38 years. It included hypertension followed by progressive renal insufficiency. No polyuria, anemia, gout, hematuria, nor proteinuria were seen. An average of 4.5 years elapsed from diagnosis to end-stage renal disease. Renal pathology at early stages of the disease showed extensive tubulointerstitial fibrosis and global glomerulosclerosis. Linkage analysis was performed at the two known loci of ADMCKD, on Chromosomes 1 and 16. Linkage to the chromosome 16 locus was excluded. However, linkage to the chromosome 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 Mb 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 characterized 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 locus.
Departments of Microbiology and Immunology, the Ben Gurion University of the Negev, Beer Sheva, Israel. ruti@bgumail.bgu.ac.il
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Parvari
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Shnaider
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Basok
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Katchko
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Borochovich
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Kanis
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Landau
D000328:Adult; D002878:Chromosomes, Human, Pair 1; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D007493:Iraq; D007585:Jews / Q000235:genetics; D007668:Kidney / Q000473:pathology; D007679:Kidney Medulla / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology