两例精子鞭毛多发形态异常男性不育症患者的DNAH1基因变异分析

Analysis of DNAH1 gene variant in two infertile males with multiple morphological abnormalities of sperm flagella

目的对2例由严重弱精子症导致原发性男性不育患者进行临床和遗传学分析,明确其可能的致病原因。方法提取患者及父母外周血基因组DNA,采用全外显子组测序技术对患者进行基因变异分析,并对疑似致病变异进行Sanger测序验证和致病性分析。结果全外显子测序显示例1 DNAH1基因存在c.2016T>G(p.Y672X)和c.6017T>G(p.V2006G)复合杂合变异;例2 DNAH1基因存在c.2610G>A(p.W870X)纯合变异,分别遗传自父亲和母亲。按照美国医学遗传学会与基因组学学会遗传变异分类标准与指南,DNAH1基因c.2016T>G(p.Y672X)和c.2610G>A(p.W870X)变异均为致病(PVS1+PM2+PM3+PP3)。结论2例患者可能均为DNAH1基因变异导致的精子鞭毛多发形态异常,进而引起原发性男性不育。

Objective To explore the clinical feature and gene variant for two cases of primary male infertility caused by severe asthenospermia and to analyze the etiology of the disease.Methods Genomic DNA of peripheral blood samples of patients and their parents was extracted and gene variation analysis of the patients was conducted by using whole exome sequencing.Suspected pathogenic variant was verified by Sanger sequencing and pathogenic analysis.Results Whole exome sequencing showed that the DNAH1 gene of patient 1 had two heterozygous variants of c.2016T>G(p.Y672X)and c.6017T>G(p.V2006G).The DNAH1 gene of patient 2 had a homozygous variant of c.2610G>A(p.W870X),which were inherited from his father and mother,respectively.According to American College of Medical Genetics and Genomics standards and guidelines,the c.2016T>G(p.Y672X)and c.2610G>A(p.W870X)varaints of DNAH1 gene were predicted to be pathogenic(PVS1+PM2+PM3+PP3).Conclusion The two patients of multiple morphological abnormalities of the sperm flagella may be caused by DNAH1 gene variant,which has resulted in primary male infertility.