先天性遗传性角膜内皮营养不良患者SLC4A11基因新突变位点的鉴定  

Identification of novel mutations of SLC4A11 gene in patients with congenital hereditary endothelial dystrophy

作　　者：黎玥 张婧 徐建江 Li Yue;Zhang Jing;Xu Jianjiang(Eye Institute and Department of Ophthalmology,Eye&ENT Hospital,Fudan University,NHC Key Laboratory of Myopia(Fudan University),Shanghai Key Laboratory of Visual Impairment and Restoration,Shanghai 200031,China)

机构地区：[1]复旦大学附属眼耳鼻喉科医院眼科,国家卫生健康委员会近视眼重点实验室,中国医学科学院近视眼重点实验室,上海200031

出　　处：《中华眼科杂志》2021年第2期133-138,共6页Chinese Journal of Ophthalmology

基　　金：国家自然科学基金(81700806,81870630)。

摘　　要：目的探讨先天性遗传性角膜内皮营养不良(CHED)患者的致病基因突变位点。方法回顾性系列病例研究。收集2017年8月至2018年9月于复旦大学附属眼耳鼻喉科医院眼科就诊的6例CHED患者进行外周血基因组DNA全外显子组测序。患者均为男性,年龄7~29岁。基于本课题组前期已建立的候选突变筛选流程进行后续基因突变分析,并根据《美国医学遗传学与基因组学学会遗传突变分类标准与指南》,结合基因功能及相关文献报道确定致病突变位点,最后经Sanger测序法验证。结果本研究对6例CHED患者进行了全外显子组测序,在其中4例患者中检测出6个不同的SLC4A11基因突变,包括4个错义突变(p.Arg869Cys、p.Pro773Leu、p.Arg869His、p.Arg755Trp),1个移码突变(p.Phe713 fs),1个剪切位点突变(c.1330+1G>T)。新发现的移码突变的致病性等级为致病,剪切位点突变的致病性不明确。结论本研究鉴定得到6个CHED相关的致病基因突变位点,其中剪切位点突变c.1330+1G>T和移码突变p.Phe713 fs为新突变。Objective To identify the potential pathogenic variants in patients with congenital hereditary endothelial dystrophy(CHED).Methods A retrospective study.Six CHED patients were recruited from the Department of Ophthalmology at the Eye and ENT Hospital of Fudan University from August 2017 to September 2018.They were all males,and were 7 to 29 years old at the time of consultation,with an average age of 20.5 years.Whole-exome sequencing was performed on the six CHED patients.The Genome Analysis Tool Kit Best Practices pipeline and an in-house bioinformatics pipeline were applied for variants analyses,according to the 2015 American College of Medical Genetics and Genomics(ACMG)guidelines.Potential pathogenic variants were further validated by Sanger sequencing.Results Six mutations in the SLC4A11 gene were identified in four out of six CHED patients,including four missense mutations(p.Arg869Cys,p.Pro773Leu,p.Arg869His,p.Arg755Trp),one frameshift mutation(p.Phe713fs),and one splicing site mutation(c.1330+1G>T).The frameshift mutation was pathogenic,while the pathogenicity of the splicing site mutation was unknown.Conclusions We identified six CHED-associated mutations in this study.The frameshift mutation(p.Phe713fs)and the splicing site mutation(c.1330+1G>T)were novel.

关 键 词：角膜营养不良 遗传性 全外显子组测序 SLC4A蛋白类 突变 

分 类 号：R772.2[医药卫生—眼科]