中国16例巴特综合征基因突变分析和治疗随访研究  

Gene analysis, treatment, and follow- up of sixteen Chinese patients with Bartter syndrome

作　　者：韩玥[1] 林毅[2] 孙清 王淑娟[1] 高延霞[4] 邵乐平[1] 

机构地区：[1]青岛大学医学院附属医院中心实验室和肾内科,266003 [2]青岛大学医学院附属医院中心实验室和儿科,266003 [3]青岛市妇女儿童医院肾脏免疫科 [4]山东大学齐鲁医院(青岛)泌尿内科

出　　处：《中华肾脏病杂志》2017年第8期573-581,共9页Chinese Journal of Nephrology

基　　金：国家自然科学基金面上项目（81170653）;山东省自然科学基金（ZR2014JL054）

摘　　要：目的对中国16例可疑巴特综合征（Barttersyndrome，BS）患者进行基因突变分析和治疗随访研究。方法通过二代测序和多重连接酶探针依赖扩增（MLPA）的方法进行突变分析。分析患者临床表现及生化特点，随访患者病情变化。结果共确定CLCNKB基因15个突变位点，其中11个新突变位点；SLC12A1基因新发现1个错义突变和1个小缺失突变；CLCNKA基因新发现1个大片段缺失突变；BSND基因发现1个已报道过的错义突变。CLCNKB全基因缺失为最常见的突变（32％），而大片段缺失突变频率高达50％。最常见的临床表现为多饮多尿（15／16）和发育迟缓（15／16），16例患者均为低钾低氯性代谢性碱中毒。吲哚美辛对生长发育有明显的改善作用。结论本研究共发现19个突变位点，其中14个新突变位点，丰富了人类基因突变库，并为中国人群遗传咨询和基因诊断的开展提供有益的借鉴。Objective To analyze the mutations of causal genes in sixteen Chinese patients with suspicious Bartter syndrome, and follow up their treatment results. Methods Mutations were identified by the next generation sequencing and the multiplex ligation-dependent probe amplification （MLPA）. Clinical and biochemical features at the first presentation as well as follow-up results were reviewed. Results 15 different CLCNKB gene mutations were identified in sixteen patients with BS, including 11 novel ones. A novel missense mutation and a novel small deletion were found from SLC12A1 gene. A novel gross deletion was found in CLCNKA gene. A recurrent missense mutation was identified from BSND gene. The whole gene deletion mutation of CLCNKB gene was the most frequent mutation （32%）, and the rate of gross deletion was up to 50 percent in this group of Chinese patients. The most common clinical manifestations were development retardation （15/16）, polydipsia and polyuria （15/16）. All of the patients were detected with hypokalemia, hypochloremia and metabolic alkalosis. Indomethacin treatment had significant improvement to the stature and weight restoration. Conclusion The present study has found 19 mutations, including 14 novel ones, which enriches the human gene mutation database （HGMD） and provides valuable references to the genetic counseling and diagnosis of Chinese population.

关 键 词：BARTTER综合征 突变 CLCNKB基因 SLCl2A1基因 BSND基因 基 因型和表型 

分 类 号：R692[医药卫生—泌尿科学]