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。n （中华眼科杂志，2021，57：133-138）“,”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.n (Chin J Ophthalmol, 2021, 57: 133-138)