Department of Andrology, United Diagnostic and Research Center for Clinical Genetics, School of Public Health & Women and Children's Hospital, Xiamen University, Xiamen, Fujian, China.
School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China.
Clin Genet. 2019 Nov;96(5):385-393. doi: 10.1111/cge.13602. Epub 2019 Jul 23.
Male patients with multiple morphological abnormalities of the sperm flagella (MMAF) are infertile and exhibit absent, short, coiled, bent and/or irregular sperm flagella. Mutations in the SPEF2 gene reduce sperm motility and cause sperm tail defects in animal models and humans. In the present study, we performed a genetic analysis on an MMAF patient and identified novel biallelic mutations in the SPEF2 gene. The biallelic mutations were confirmed by Sanger sequencing and in silico analysis revealed that, these variations were deleterious. The expression of truncated SPEF2 protein was reduced significantly in the patient's spermatozoa. The spermatozoa harbored biallelic mutations and showed severe ultrastructural defects in the axoneme and mitochondrial sheath. Our data suggest that biallelic mutations in SPEF2 can cause severe sperm flagellum defects, thus providing a novel candidate genetic pathogen for the human MMAF phenotype.
患有多种精子鞭毛形态异常（MMAF）的男性患者不育，表现为精子鞭毛缺失、短小、卷曲、弯曲和/或不规则。SPEF2 基因突变会降低精子的运动能力，并导致动物模型和人类的精子尾部缺陷。在本研究中，我们对一名 MMAF 患者进行了基因分析，发现 SPEF2 基因存在新的双等位基因突变。双等位基因突变通过 Sanger 测序得到确认，并且通过计算机分析显示，这些变异是有害的。患者精子中的截断 SPEF2 蛋白表达显著降低。精子携带有双等位基因突变，并显示出轴丝和线粒体鞘的严重超微结构缺陷。我们的数据表明，SPEF2 的双等位基因突变可导致严重的精子鞭毛缺陷，从而为人类 MMAF 表型提供了一个新的候选遗传病因。
