Owing to less than 1% of motile spermatozoa in the ejaculated semen, severe asthenozoospermia is a serious threat to the male reproductive health. Herein, we identified a novel homozygous variant in CCDC9 (NC_000019.9: g.47763960C>T, NM_015603.3, NP_056418.1: p. Ser109Leu) in a patient from a consanguineous family. The variant was highly pathogenic and was predicted to be a candidate gene for asthenozoospermia through in silico analysis. The CCDC9 protein levels were significantly low and its morphology and ultrastructure were severely damaged in the spermatozoa containing the novel variant. Therefore, CCDC9 may be a novel pathogenic gene associated with severe asthenozoospermia.

Abbreviations: CCDC9: coiled-coil domain containing 9; AZS: asthenozoospermia; MP: midpiece; MS: mitochondrial sheath; ODF: outer dense fiber; CP: central pair; DMT: doublet microtubule; IDA: inner dynein arm; ODA: outer dynein arm.

由于精液中运动精子的比例不到1％，严重的弱精子症对男性生殖健康构成严重威胁。在本文中，我们在近亲家庭的患者中在CCDC9（NC_000019.9：g.47763960C> T，NM_015603.3，NP_056418.1：p。Ser109Leu）中鉴定了一个新的纯合变异体。该变异体具有高致病性，通过计算机分析可以预测其是弱精子症的候选基因。在含有新变异体的精子中，CCDC9的蛋白质水平非常低，其形态和超微结构受到严重破坏。因此，CCDC9可能是与严重的弱精子症相关的新型致病基因。

缩写：CCDC9：包含9的卷曲螺旋域；AZS：弱精子症；MP：中音；MS：线粒体鞘；ODF：外部致密纤维；CP：中央对；DMT：双胞胎微管；IDA：内达因臂；ODA：外部达因臂。