Scolari F, Puzzer D, Amoroso A, Caridi G, Ghiggeri G M, Maiorca R, Aridon P, De Fusco M, Ballabio A, Casari G
Division and Chair of Nephrology, Spedali Civili and University of Brescia, Brescia, Italy.
Am J Hum Genet. 1999 Jun;64(6):1655-60. doi: 10.1086/302414.
Autosomal dominant medullary cystic disease (ADMCKD) is an interstitial nephropathy that has morphologic and clinical features similar to autosomal recessive nephronophthisis. The typical renal dysfunction associated with ADMCKD results mainly from a defect in urinary concentration ability, although results of urinalysis are normal. Recently, a locus on chromosome 1 was associated with ADMCKD, in DNA from two large Cypriot families, and genetic heterogeneity was inferred. We describe the genomewide linkage mapping of a new locus for medullary cystic disease, ADMCKD2, on chromosome 16p12 in a four-generation Italian pedigree. The family with ADMCKD2 fulfills the typical diagnostic criteria of ADMCKD, complicated by hyperuricemia and gouty arthritis. Marker D16S3036 shows a maximum two-point LOD score of 3.68, and the defined critical region spans 10.5 cM, between D16S500 and SCNN1B1-2. Candidate genes included in the critical region are discussed.
常染色体显性遗传性髓质囊性肾病（ADMCKD）是一种间质性肾病，其形态学和临床特征与常染色体隐性遗传性肾单位肾痨相似。与ADMCKD相关的典型肾功能障碍主要源于尿液浓缩能力缺陷，尽管尿液分析结果正常。最近，在来自两个塞浦路斯大家族的DNA中，1号染色体上的一个位点与ADMCKD相关，由此推断存在遗传异质性。我们描述了在一个四代意大利家系中，16号染色体p12上一个新的髓质囊性疾病位点ADMCKD2的全基因组连锁图谱。患有ADMCKD2的这个家系符合ADMCKD的典型诊断标准，并伴有高尿酸血症和痛风性关节炎。标记物D16S3036显示最大两点LOD评分为3.68，定义的关键区域跨度为10.5厘摩，位于D16S500和SCNN1B1 - 2之间。文中讨论了关键区域内的候选基因。
