Hildebrandt F, Strahm B, Nothwang H G, Gretz N, Schnieders B, Singh-Sawhney I, Kutt R, Vollmer M, Brandis M
University Children's Hospital, Freiburg University, Freiburg, Germany.
Kidney Int. 1997 Jan;51(1):261-9. doi: 10.1038/ki.1997.31.
Familial juvenile nephronophthisis (NPH), an autosomal recessive cystic disease of the kidney, is the most common genetic cause of end-stage renal disease (ESRD) in the first two decades of life. A gene locus for nephronophthisis type 1 (NPH1) has been mapped by linkage analysis to chromosome 2q13. We performed a haplotype analysis in 16 NPH families with at least two affected patients with the typical history, clinical signs and histology of NPH using microsatellite markers of the NPH1 genetic region. By demonstration of a recombinant event marker D2S1893 was identified as a novel centromeric flanking marker to the NPH1 critical genetic region. Absence of linkage to the NPH1 locus in six NPH families confirmed the existence of at least one additional gene locus for NPH. Linkage to the NPH1 locus was demonstrated in 10 families. In 8 of these families a homozygous deletion was identified. These data permit for the first time the study of the development of renal failure in a subset of NPH1 families, which is most likely homogeneous with regard to the responsible gene locus. We present a statistical description of serial serum creatinine measurements in NPH1. Analysis of renal death revealed a median of 13.1 years. Age-dependent quartiles were generated for serum creatinine. In summary, the new marker provides a diagnostic tool to aid in the diagnosis of NPH, while the progression charts offer a standard for an assessment of the rate of progression to ESRD for patients with NPH1 to be used in future therapeutic trials and for a prediction of the individual course of the disease.
家族性青少年肾单位肾痨（NPH）是一种常染色体隐性遗传性肾脏囊性疾病，是20岁前终末期肾病（ESRD）最常见的遗传病因。1型肾单位肾痨（NPH1）的基因位点已通过连锁分析定位于2号染色体q13区。我们利用NPH1基因区域的微卫星标记，对16个NPH家族进行了单倍型分析，这些家族中至少有两名患者具有典型的NPH病史、临床体征和组织学表现。通过证明一个重组事件，标记D2S1893被确定为NPH1关键基因区域的一个新的着丝粒侧翼标记。六个NPH家族与NPH1位点无连锁关系，证实至少存在一个额外的NPH基因位点。在10个家族中证明了与NPH1位点的连锁关系。在其中8个家族中发现了纯合缺失。这些数据首次允许对一部分NPH1家族中肾衰竭的发展进行研究，就致病基因位点而言，这部分家族很可能是同质的。我们给出了NPH1患者系列血清肌酐测量值的统计学描述。对肾衰竭死亡情况的分析显示，中位数为13.1年。生成了血清肌酐的年龄依赖性四分位数分布。总之，新的标记物提供了一种诊断工具，有助于NPH的诊断，而病程进展图为评估NPH1患者进展至ESRD的速率提供了一个标准，可用于未来的治疗试验以及预测个体疾病进程。
