Haider N B, Carmi R, Shalev H, Sheffield V C, Landau D
Department of Pediatrics, Division of Medical Genetics, University of Iowa, Iowa City, IA 52242, USA.
Am J Hum Genet. 1998 Nov;63(5):1404-10. doi: 10.1086/302108.
A novel type of infantile nephronophthisis was identified in an extended Bedouin family from Israel. This disease has an autosomal recessive mode of inheritance, with the phenotypic presentation ranging from a Potter-like syndrome to hyperechogenic kidneys, renal insufficiency, hypertension, and hyperkalemia. Affected individuals show rapid deterioration of kidney function, leading to end-stage renal failure within 3 years. Histopathologic examination of renal tissue revealed variable findings, ranging from infantile polycystic kidneys to chronic tubulointerstitial nephritis, fibrosis, and cortical microcysts. A known familial juvenile nephronophthisis locus on chromosome 2q13 and autosomal recessive polycystic kidney disease on chromosome 6p21.1-p12 were excluded by genetic linkage analysis. A genomewide screen for linkage was conducted by searching for a locus inherited by descent in all affected individuals. Pooled DNA samples from parents and unaffected siblings and individual DNA samples from four affected individuals were used as PCR templates with trinucleotide- and tetranucleotide-repeat polymorphic markers. Using this approach, we identified linkage to infantile nephronophthisis for markers on chromosome 9q22-31. The disorder maps to a 12.9-cM region flanked by markers D9S280 and GGAT3G09.
在一个来自以色列的贝都因大家族中发现了一种新型婴儿型肾单位肾痨。这种疾病为常染色体隐性遗传模式，其表型表现从波特样综合征到肾回声增强、肾功能不全、高血压和高钾血症不等。患病个体肾功能迅速恶化，在3年内发展为终末期肾衰竭。肾组织的组织病理学检查结果各异，从婴儿型多囊肾到慢性肾小管间质性肾炎、纤维化和皮质微囊肿。通过基因连锁分析排除了位于2q13的已知家族性青少年肾单位肾痨位点和位于6p21.1 - p12的常染色体隐性多囊肾病。通过在所有患病个体中寻找一个由遗传获得的位点进行全基因组连锁筛查。来自父母和未患病兄弟姐妹的混合DNA样本以及来自四个患病个体的个体DNA样本用作含有三核苷酸和四核苷酸重复多态性标记的PCR模板。采用这种方法，我们确定了位于9q22 - 31上的标记与婴儿型肾单位肾痨存在连锁关系。该疾病定位于由标记D9S280和GGAT3G09界定的一个12.9厘摩区域。
