Ⅰ型Bartter综合征新发剪切位点突变分析及文献复习  

Novel splicing mutation in type Ⅰ Bartter syndrome and review of the literature

作　　者：谢彦舒 钟京梓[1] 廖海霞[1] 官红林 蓝丹[1] 

机构地区：[1]广西医科大学第一附属医院儿科,南宁530021

出　　处：《广西医科大学学报》2018年第2期185-189,共5页Journal of Guangxi Medical University

基　　金：广西医科大学第一附属医院眼国人员院内科启动基金(No.201001)

摘　　要：目的:对Ⅰ型Bartter综合征家系剪切位点纯合突变的临床特点及基因检测结果进行分析,从基因水平上明确该病诊断,并探讨该病的致病机制。方法:收集1例Ⅰ型Bartter综合征患儿及家系临床资料,通过二代基因测序检测含SLC12A1、KCNJ1、CLCNKB、BSND、CASR、SLC12A3等基因在内270个相关基因,用Sanger测序对筛查出来的可能致病突变位点进行家系验证,通过软件及查阅文献对突变位点致病性进行分析。结果:先证者临床表现为消瘦乏力、多饮多尿、生长发育落后、低血钾、代谢性碱中毒及高醛固酮血症,测序结果显示:SLC12A1基因c.1786+2T>C剪切位点纯合突变,其父为无症状杂合突变携带者,其母和哥哥未发现变异。查阅文献发现先证者临床表现符合Bartter综合征且SLC12A1基因为Ⅰ型Bartter综合征的致病基因,检索db SNP数据库、Clin Var数据库、HGMD数据库、Pubmed、中国知网等国内外文献数据库均未发现该突变位点报道。同时,Poly Phen-2、SIFT和MutationTaster 5软件分析预测该突变可能为致病性突变。综合分析临床表型和基因结果该先证者可诊断为Ⅰ型Bartter综合征,且其c.1786+2T>C剪切位点纯合突变为新发致病性突变。结论:本文首次报道c.1786+2T>C突变为新发致病性剪切位点纯合突变,扩展了SLC12A1基因突变谱,为Bartter综合征的临床诊断和遗传咨询提供帮助,并为进一步探索其致病机制提供一定的理论基础。Objective： We aimed to define the comprehensive diagnosis of type I Bartter syndrome by analyzing a case with a novel splicing homozygous mutation and to discuss the pathogenic mechanism. Methods： The clin- ical data of the proband were collected. A Next Generation Sequencing （containing 270 selected related genes, such as SLC12A1, KCNJ1, CLCNKB, BSND CASR and SLC12A3） was performed in the proband. Sanger se- quencing was used to validate the mutation in the proband and the family members. Then analyzed the pathoge- nicity of the mutation. Results： The proband manifested hypokalemic metabolic alkalosis, hyperaldosteronemia, fatigue, polyuria and polydipsia. A novel splicing homozygous mutation c. 1786 ＋ 2T〉C in SLC12A1 gene was identified to be the genetic cause of type I Bartter syndrome in this family. His father was asymptomatic hetero- zygous carrier, mother and brother were normal. The mutation had not been reported in dbSNP Database, Clin- Vat Database, Human Gene Mutation Database, Pubmed and CNKI. PolyPhen-2, SIFT and MutationTaster5 pre- dicted that the mutation was possibly pathogenic. Summarizing the clinical symptoms and genetic results, the pro- band was diagnosed as type I Bartter syndrome and the mutation site c. 1786＋2T〉C was a novel splicing homo- zygous pathogenic mutation. Conclusion： This is the first report of a novel splicing homozygous mutation c. 1786 ＋ 2T〉C in SLC 12A1 gene. This paper not only extends current knowledge of the mutation spectrum of the SLC12A1 gene associated with type 1 Bartter snydrome, but also contributes to the clinical diagnosis and genetic counseling of Bartter syndrome and provides a solid theoretical basis for exploring the pathogenic mechanism.

关 键 词：BARTTER综合征 SLC12A1基因 NKCC2 新发突变 剪切突变 

分 类 号：R597[医药卫生—内科学]