<i>CCDC9</i> is identified as a novel candidate gene of severe asthenozoospermia

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 <i>CCDC9</i> (NC_000019.9: g.47763960C&gt;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 <i>in silico</i> analysis. The CCDC9 protein levels were significantly low and its morphology and ultrastructure were severely damaged in the spermatozoa containing the novel variant. Therefore, <i>CCDC9</i> may be a novel pathogenic gene associated with severe asthenozoospermia. <b>Abbreviations</b>: <i>CCDC9</i>: 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.由于射出精液中活动精子占比不足1%，重度弱精子症（severe asthenozoospermia）对男性生殖健康构成严重威胁。本研究从一个近亲婚配家族的患者体内，鉴定到<i>CCDC9</i>（卷曲螺旋结构域包含蛋白9，coiled-coil domain containing 9）基因上一处全新的纯合变异：NC_000019.9: g.47763960C>T、NM_015603.3、NP_056418.1: p.Ser109Leu。该变异具有高度致病性，通过<i>in silico</i>计算机模拟分析预测，<i>CCDC9</i>可作为弱精子症的候选致病基因。携带该新型变异的精子中，CCDC9蛋白表达水平显著降低，其形态与超微结构均遭到严重破坏。因此，<i>CCDC9</i>或可成为与重度弱精子症相关的新型致病基因。<b>缩略词说明</b>：<i>CCDC9</i>：卷曲螺旋结构域包含蛋白9（coiled-coil domain containing 9）；AZS：弱精子症（asthenozoospermia）；MP：精子中段（midpiece）；MS：线粒体鞘（mitochondrial sheath）；ODF：外致密纤维（outer dense fiber）；CP：中央微管对（central pair）；DMT：双联微管（doublet microtubule）；IDA：内动力臂（inner dynein arm）；ODA：外动力臂（outer dynein arm）。