Department of Ophthalmology, Xiang'an Hospital of Xiamen University; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science; Fujian Engineering and Research Center of Eye Regenerative Medicine; Eye Institute of Xiamen University; School of Medicine, Xiamen University, Xiamen, Fujian, China.
Jiaen Genetics Laboratory, Beijing Jiaen Hospital, Beijing, China.
DNA Cell Biol. 2021 Jun;40(6):833-840. doi: 10.1089/dna.2021.0097. Epub 2021 May 14.
Sperm motility is vital to human reproduction, and malformed sperm flagella can cause male infertility. Individuals with multiple morphological abnormalities of the flagella mostly have absent, short, coiled, bent, and/or irregular-caliber flagella. In this study, a patient with male infertility underwent a physical examination along with his wife. Genetic testing was performed by whole-exome sequencing of the couple, and Sanger sequencing was performed for validation. Novel biallelic variations in the : (NM_015512.4) gene consisting of c.1336G>C (p.E446Q) and c.2912G>A (p.R971H) were identified. structural analysis revealed that the amino acid residues affected by the variation were evolutionarily conserved, and the variant p.R971H influenced the stability of the DNAH1 protein. Morphological studies of the patient's sperm showed defects in its flagella. Results of Papanicolaou staining and scanning electron microscopy demonstrated coiled and short flagella with multiple anomalies. Transmission electron microscopy of the sperm flagella showed that the inner dynein arm and radial spoke were absent, and the dense fiber and microtubule doublets were displaced. Quantitative PCR of the mRNA of the patient's sperm showed that the expression of was dramatically reduced. Collectively, these findings elucidated the genetic cause of the family's infertility and provided insight into the functioning of the gene.
精子运动能力对人类生殖至关重要，畸形的精子鞭毛可导致男性不育。大多数具有鞭毛多种形态异常的个体的鞭毛缺失、短小、卷曲、弯曲和/或粗细不均。在这项研究中，一名男性不育患者与其妻子接受了体检。对夫妻双方进行全外显子组测序进行基因检测，并进行 Sanger 测序进行验证。在 : (NM_015512.4) 基因中发现了新型双等位基因变异，包括 c.1336G>C (p.E446Q) 和 c.2912G>A (p.R971H)。结构分析表明，受变异影响的氨基酸残基在进化上是保守的，变体 p.R971H 影响 DNAH1 蛋白的稳定性。患者精子的形态学研究显示其鞭毛存在缺陷。巴氏染色和扫描电子显微镜结果显示卷曲和短小的鞭毛有多种异常。精子鞭毛的透射电子显微镜显示内臂和辐条缺失，致密纤维和微管二联体移位。患者精子 mRNA 的定量 PCR 显示 的表达显著降低。综上所述，这些发现阐明了该家族不育的遗传原因，并深入了解了 基因的功能。
