Dent病4例临床及基因分析

Clinical and genetic analysis of Dent disease in 4 Chinese children

摘要:

目的研究Dent病患儿的临床及基因资料,提高对该病的认识。方法对4例Dent病患儿的临床资料、肾脏病理及基因检测的结果进行回顾性分析。结果 4例患儿均为男孩。例1~3首发表现为Fanconi综合征,例4首发表现为蛋白尿。4例均有低分子尿蛋白增高、高钙尿症,其中血尿3例,肾结石1例,肾钙质沉着2例,低磷血症3例,佝偻病3例。在例1、2、4共发现了3个位于CLCN5基因突变,包括2个缺失突变和1个无义突变,分别为exon 6-7del、c.785_787del(p.263del Leu)和c.1039 C>T(p.Arg347Term),其中前2个是新突变。结论有蛋白尿的患儿应完善尿蛋白成分检查;合并存在高尿钙或肾钙质沉着或肾结石等的Fanconi综合征的患儿,应考虑到Dent病可能;基因检测有利于临床的精准诊断。

Abstract:

Objective To study the clinical features and gene mutations of 4 Chinese children with Dent disease. Methods The clinical and laboratory data of 4 children with Dent disease were analyzed retrospectively. Genetic testing of the 4 cases was carried out. Results All of 4 cases were boys. The first impression of Cases 1-3 was Fanconi syndrome. Proteinuria was presented as the first impression in Case 4. All 4 boys presented with low-molecular weight proteinuria (LMWP) and hypercalciuria, including 3 cases with hematuria, 1 case with kidney stones, 2 cases with nephrocalcinosis, 3 cases with hypophosphatemia, and 3 cases with rickets. Mutations of the CLCN5 gene were revealed in three patients (Cases 1, 2 and 4), including exon 6-7del, c.785_787de l(p.263del Leu) and c.1039 C>T (p.Arg347Term). The first two gene mutations had never reported before. Conclusions Urine protein electrophoresis should be carried out for patients with proteinuria. Dent disease should be taken into consideration when patients with Fanconi syndrome have hypercalciuria, nephrocalcinosis or kindey stones. Genetic analyses are needed for a definite diagnosis.