Medhioub M, Cherif D, Benessy F, Silbermann F, Gubler M C, Le Paslier D, Cohen D, Weissenbach J, Beckmann J, Antignac C
INSERM U192, Hôpital Necker-Enfants Malades, Paris, France.
Genomics. 1994 Jul 15;22(2):296-301. doi: 10.1006/geno.1994.1387.
Familial juvenile nephronophthisis (NPH) is an autosomal recessive progressive tubulo-interstitial kidney disorder, responsible for 6-10% of end-stage renal failure in children, and is frequently associated with Leber amaurosis (termed Senior-Løken syndrome). The biochemical basis of NPH is unknown. We recently reported linkage of the purely renal form of NPH to three markers on chromosome 2. Our results also suggested the existence of genetic heterogeneity between NPH and SLS. To map this NPH gene more precisely, we have now tested the segregation of six new microsatellite markers and five additional families. Haplotype analyses show unequivocally that four NPH families are not linked to the chromosome 2 markers, although there are no clinical or pathological features discernible in these families that could separate them from the families linked to the chromosome 2 NPH locus (NPH1). This reveals genetic heterogeneity in the purely renal form of NPH. In situ hybridization of YAC clones isolated with two closely linked markers assigned the NPH1 region to 2q13. Furthermore, based on haplotype analysis and specific recombination events, the NPH1 gene has been placed between D2S293/D2S340 and D2S121, a genetic interval of about 5-7 cM.
家族性青少年肾单位肾痨（NPH）是一种常染色体隐性进行性肾小管间质性肾脏疾病，占儿童终末期肾衰竭病例的6%至10%，且常与莱伯先天性黑蒙（称为Senior-Løken综合征）相关。NPH的生化基础尚不清楚。我们最近报道了纯肾型NPH与2号染色体上的三个标记的连锁关系。我们的结果还提示NPH和SLS之间存在遗传异质性。为了更精确地定位这个NPH基因，我们现在检测了六个新的微卫星标记以及另外五个家系的分离情况。单倍型分析明确显示，四个NPH家系与2号染色体标记不连锁，尽管在这些家系中没有可辨别出的临床或病理特征能将它们与与2号染色体NPH位点（NPH1）连锁的家系区分开来。这揭示了纯肾型NPH的遗传异质性。用两个紧密连锁的标记分离出的YAC克隆的原位杂交将NPH1区域定位于2q13。此外，基于单倍型分析和特定的重组事件，NPH1基因已被定位在D2S293/D2S340和D2S121之间，这是一个约5至7厘摩的遗传区间。
