Institute of Health and Medicine, Hefei Comprehensive National Science Center, Division of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
Asian J Androl. 2024 Nov 1;26(6):605-609. doi: 10.4103/aja202432. Epub 2024 Jun 11.
Male infertility is a worldwide health issue, affecting 8%-12% of the global population. Oligoasthenoteratozoospermia (OAT) represents a severe type of male infertility, characterized by reduced sperm count and motility and an increased frequency of sperm with aberrant morphology. Using whole-exome sequencing, this study identified a novel missense mutation (c.848C>A, p.A283E) in the coiled-coil domain-containing 34 gene (CCDC34) in a consanguineous Pakistani family. This rare mutation was predicted to be deleterious and to affect the protein stability. Hematoxylin and eosin staining of spermatozoa from the patient with OAT revealed multiple morphological abnormalities of the flagella and transmission electron microscopy indicated axonemal ultrastructural defects with a lack of outer dynein arms. These findings indicated that CCDC34 plays a role in maintaining the axonemal ultrastructure and the assembly or stability of the outer dynein arms, thus expanding the phenotypic spectrum of CCDC34 missense mutations.
男性不育是一个全球性的健康问题，影响着全球 8%-12%的人口。少弱畸形精子症（OAT）是一种严重的男性不育症，其特征是精子数量和活力减少，畸形精子频率增加。本研究通过全外显子组测序，在一个巴基斯坦的近亲家庭中发现了一个位于卷曲螺旋结构域蛋白 34 基因（CCDC34）中的新型错义突变（c.848C>A，p.A283E）。该罕见突变被预测为有害性的，会影响蛋白质稳定性。对 OAT 患者的精子进行苏木精和伊红染色显示鞭毛有多种形态异常，透射电子显微镜显示轴丝超微结构缺陷，缺少外周动力蛋白臂。这些发现表明 CCDC34 在维持轴丝超微结构以及外周动力蛋白臂的组装或稳定性方面发挥作用，从而扩展了 CCDC34 错义突变的表型谱。
