Parvari R, Shnaider A, Basok A, Katchko L, Borochovich Z, Kanis A, Landau D
Departments of Microbiology and Immunology, the Ben Gurion University of the Negev, Beer Sheva, Israel.
Am J Med Genet. 2001 Mar 15;99(3):204-9. doi: 10.1002/1096-8628(2001)9999:9999<::aid-ajmg1158>3.0.co;2-p.
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.
成年起病、无肉眼可见囊肿且呈进行性恶化的常染色体显性遗传性肾病包括髓质囊性肾病（ADMCKD）以及其他不太特异的类型。我们研究了一个犹太裔家族，其中15名成员（男女皆有）患有慢性肾衰竭。肾脏受累的首个证据出现在18至38岁之间。表现为高血压，随后是进行性肾功能不全。未观察到多尿、贫血、痛风、血尿或蛋白尿。从诊断到终末期肾病平均历时4.5年。疾病早期的肾脏病理显示广泛的肾小管间质纤维化和全球肾小球硬化。在ADMCKD的两个已知基因座（位于1号和16号染色体）进行了连锁分析。排除了与16号染色体基因座的连锁。然而，与ADMCKD的1q21染色体基因座建立了连锁关系，与D1S394的最大两点LOD评分为3.82。疾病区间可缩小至D1S1156和D1S2635之间约9厘摩/7.4兆碱基。多点连锁分析显示最大LOD为4.21，从标记D1S2858和D1S2624出现一个宽峰。本报告确立了一种以高血压和进行性肾衰竭为特征的家族性肾病与ADMCKD所描述基因座之间的连锁关系，ADMCKD是一种典型地与肉眼可见的皮质髓质囊肿、失盐性肾小管间质性肾病和贫血相关的疾病。这一发现拓宽了位于1q21染色体基因座的ADMCKD的临床谱。
