Mutations in the CLCN5 gene in Japanese patients with familial idiopathic low-molecular-weight proteinuria.
Mutations in the CLCN5 gene in Japanese patients with familial idiopathic low-molecular-weight proteinuria.
复制标题
日本家族性特发性低分子量蛋白尿患者的 CLCN5 基因突变。
作者：
H. Nakazato;S. Hattori;A. Furuse;T. Kawano;S. Karashima;M. Tsuruta;J. Yoshimuta;F. Endo;I. Matsuda
家族性特发性低分子蛋白尿(FILMWP)是一种主要发生在男性的肾脏近端小管病变。FILMWP的特点是轻度蛋白尿，包括低分子蛋白尿、氨基酸尿和相对保守的肾功能，但没有软骨病。为了确定FILMWP是否与CLCN5基因有关，CLCN5基因与登特氏病和两种相关疾病有关，我们分析了四个FILMWP日本家系的CLCN5基因。我们发现了两个新的突变：一个是外显子10的520个丝氨酸密码子的单碱基插入，另一个是外显子8的403个酪氨酸密码子的单碱基缺失。这些突变导致阅读框架的改变，导致截短的CLC5蛋白的合成分别缺少220个(29%)和314个(42%)氨基酸。这些突变分别在两个家系中被证明与疾病共分离。我们得出结论，CLCN5基因与一些日本家庭的近端肾小管病变有关，而FILMWP可能是登特氏病的一个变种。
Familial idiopathic low-molecular-weight proteinuria (FILMWP) is a renal proximal tubulopathy that occurs predominantly in males. FILMWP is characterized by mild proteinuria consisting of low-molecular-weight proteinuria, aminoaciduria and relatively conserved renal function, but without rickets. To determine whether FILMWP is related to the CLCN5 gene, which is responsible for Dent's disease and two related disorders, we analyzed the CLCN5 gene from four Japanese families with FILMWP. We identified two novel mutations: one was a single base insertion at codon 520 serine in exon 10 and the other was a single base deletion at codon 403 tyrosine in exon 8. These mutations caused a shift in the reading frame, resulting in synthesis of truncated CLC5 proteins that lacked 220 (29%) and 314 (42%) amino acids, respectively. These mutations were demonstrated to cosegregate with the disease in two families, respectively. We conclude that the CLCN5 gene is responsible for this proximal renal tubulopathy in some Japanese families and that FILMWP is possibly a variant of Dent's disease.