少汗型外胚叶发育不全新EDA胶原结构域整码缺失突变基因型与表型分析

Phenotypic analysis of novel EDA collagen domain mutations in a family with hypohidrotic ectodermal hypoplasia

目的:寻找1例中国汉族少汗型外胚叶发育不全(HED)患者及其核心家系的致病基因。方法:收集1例HED患者及家系资料,采集先证者、核心家系及对照组成员外周血进行全外显子组测序(WES),采用Sanger测序验证突变基因,对突变EDA位点进行保守性分析,根据《美国医学遗传学与基因组学学会(ACMG)遗传变异分类标准与指南》评估该突变的致病性。结果:先证者中存在一个新的EDA基因突变(参考序列NM_001399.5):c.559_576delCCTCCAGGACCCCCAGGA,该突变导致第187位至第192位氨基酸缺失(p.187_192del),为整码缺失突变。患儿母亲同一位置呈现杂合双峰,患儿父亲及对照组未检测到此突变。结论:缺失突变c.559_576delCCTCCAGGACCCCCAGGA是导致该例HED临床表型的主要原因,该突变位点扩大了EDA基因突变谱。

Objective: To detect the EDA gene mutation in a pedigree with X-linked ectodermal dysplasia. Methods: Data were collected from one hypohidrotic ectodermal hypoplasiac(HED) patient and family. Peripheral blood was collected from the HED patient, core family members and control group members for whole-exome sequencing(WES). Sanger sequencing was used to verify the mutated gene, the mutated EDA was analyzed for conservativeness, and the pathogenicity of the mutation was assessed according to the American College of Medical Genetics and Genomics(ACMG) Classification Criteria and Guidelines for Genetic Variants. Results: A novel EDA gene mutation(reference sequence NM_001399.5) was present in the proband: c.559_576delCCTCCAGGACCCCCCCAGGA, which resulted in a deletion of amino acids from position 187 to position 192(p.187_192del). The patient’s mother carried the same position showing heterozygous bimodal peak, and this mutation was not detected in the patient’s father and control group. Conclusion: A novel EDA nonframeshift deletion mutation is identified, which extends the mutation spectrum of EDA gene.