背景:Dent病是一种X连锁遗传性肾小管疾病,以蛋白尿为特征,高钙尿症,肾钙化病,肾结石,病,和终末期肾病.几乎60%的患者在CLCN5基因(Dent1)中具有致病突变,和15%的受影响的个体在OCRL1基因突变(Dent2)。这项研究的目的是在患有Dent病的伊朗家庭中鉴定CLCN5突变,并表征相关的临床综合征。
方法:我们研究了来自13个无关的伊朗家庭的14例患者,这些患者的临床诊断为Dent病。所有患者均检测到蛋白尿。5例患者发现肾结石,血尿2例。大多数受影响的个体患有肾钙化病。对所有14例患者进行了CLCN5基因的PCR测序。我们还对一名未发现致病突变的患者进行了下一代测序(NGS)。
结果:我们鉴定了四种不同的CLCN5突变,包括一种错义突变(c.731C>T),一个无义突变(c.100C>T),和两个新的突变,由一个移码突变(c.1241_1242dupAA)和一个剪接突变(c.805-2A>G)组成。我们还鉴定了一个OCRL1突变,一个剪接突变(c.1466+1G>A),使用NGS。
结论:这是首次描述伊朗登特病患者CLCN5基因突变的报告,并通过报告两个新的突变来扩大CLCN5突变的范围。c.1241_1242dupAA和c.805-2A>G.
Dent\'s disease is an X-linked inherited renal tubular disorder characterized by proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, rickets, and end-stage renal disease. Almost 60% of patients have causative mutations in the CLCN5 gene (Dent 1), and 15% of affected individuals have mutations in the OCRL1 gene (Dent 2). The aims of this
study are to identify CLCN5 mutations in Iranian families with Dent\'s disease and to characterize the associated clinical syndromes.
We studied 14 patients from 13 unrelated Iranian families with a clinical diagnosis of Dent\'s disease. Proteinuria was detected in all patients. Nephrolithiasis was found in 5 patient, and hematuria in 2 patients. Most of the affected individuals had nephrocalcinosis. PCR-sequencing for the CLCN5 gene was performed in all 14 patients. Next-generation sequencing (NGS) has also been performed in one patient who we did not find causative mutation.
We identified four different CLCN5 mutations including one missense mutation (c.731C>T), one nonsense mutation (c.100C>T), and two novel mutations, consisting of one frameshift mutation (c.1241_1242dupAA) and one splicing mutation (c.805-2A>G). We also identified one OCRL1 mutation, one splicing mutation (c.1466 + 1G>A), using NGS.
This is the first report to characterize mutations in the CLCN5 gene in Iranian patients with Dent\'s disease and expands the spectrum of CLCN5 mutations by reporting two novel mutations, c.1241_1242dupAA and c.805-2A>G.