Genetic analysis of transporters and channels related to urolithiasis or hydronephrosis

在本项目中，我们进行了以下三个与尿石症相关的研究：(1)特发性高钙尿症患者ECaC1(上皮性钙通道1)基因的遗传分析(2)遗传性低尿症患者的hURAT1(人尿酸转运蛋白1)基因分析(3)登特氏病患者的CLCN5(氯离子通道5)基因分析。在两年的调查中，我们没有检测到特发性高钙尿症患儿ECaC1基因的任何突变。(2)我们对7个无血缘关系的日本肾结石患者进行了基因分析。我们在6个家系中发现了hURAT1突变，在5个家系中检测到了W258X突变。这一结果表明W258X突变是日本肾性低尿酸血症患者的主要遗传原因。(3)我们对15多个登特氏病家系进行了CLCN5基因分析，发现了几个突变。现在，我们继续进行CLCN5和hURAT1的基因分析。本研究结果增加了对尿石症遗传背景的一定认识。

In this project, we performed the following three investigations related to urolithiasis.(1) Genetic analysis of ECaC1 (epithelial calcium channnel 1) gene in patients with idiopathic hypercalciuria(2) Genetic analysis of hURAT1 (human uirnc acid transporter 1) gene in patients with hereditary hypouricemia(3) Genecitc analysis of CLCN5 (chloride channel 5) in patients with Dent's disease.During 2 years of investigation, we could obtain the following results :(1) We could not detect any mutations in ECaC1 gene in patiesnts with idiopathic hypercalciuria who developed urolithiasis during infancy.(2) We performed genecic analyzes in 7 unrelated Japanese families with renal hypouricemia. We identified hURAT1 mutations in 6 families ; in five families, W258X mutation was detected. This result indicates that W258X mutation is the predominant genetic cause in Japanese patients with renal hypouricemia.(3) We performed CLCN5 gene analysis in more than 15 families with Dent's disease, and identified several mutations.Now, we continue to perform genetic analysis of CLCN5 and hURAT1. The present results added certain knowledge on the genetic backgrounds of urolithiasis.