Yu Xuehui, Yuan Lamei, Deng Sheng, Xia Hong, Tu Xiaolong, Deng Xiong, Huang Xiangjun, Cao Xiao, Deng Hao
Health Management Center, The Third Xiangya Hospital, Central South University, Changsha, China.
Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.
Front Genet. 2022 May 27;13:862292. doi: 10.3389/fgene.2022.862292. eCollection 2022.
The formation of left-right asymmetry of the visceral organs is a conserved feature of the human body, and the asymmetry specification of structure and function is precisely orchestrated by multiple regulatory mechanisms. The abnormal results of organ positioning situs arise from defective cilia structure or function during embryogenesis in humans. In this study, we recruited two unrelated Han-Chinese families with left-right asymmetry disorders. The combination of whole-exome sequencing and Sanger sequencing identified two compound heterozygous variants: c.4109C>T and c.9776C>T, and c.612C>G and c.8764C>T in the dynein axonemal heavy chain 17 gene () in two probands with left-right asymmetry disorders. We report for the first time a possible association between gene variants and left-right asymmetry disorders, which is known as a causal gene for asthenozoospermia. Altogether, the findings of our study may enlarge the gene variant spectrum in human left-right asymmetry disorders, pave a way to illustrate the potential pathogenesis of ciliary/flagellar disorders, and provide supplementary explanation for genetic counseling.
内脏器官左右不对称的形成是人体的一个保守特征，结构和功能的不对称特化是由多种调控机制精确编排的。在人类胚胎发育过程中，器官定位 situs 的异常结果源于纤毛结构或功能的缺陷。在本研究中，我们招募了两个患有左右不对称障碍的无关汉族家庭。全外显子组测序和桑格测序相结合，在两名患有左右不对称障碍的先证者中，于动力蛋白轴丝重链 17 基因（）中鉴定出两个复合杂合变体：c.4109C>T 和 c.9776C>T，以及 c.612C>G 和 c.8764C>T。我们首次报道了 基因变体与左右不对称障碍之间可能存在的关联，该基因是弱精子症的一个致病基因。总之，我们的研究结果可能会扩大人类左右不对称障碍中的 基因变体谱，为阐明纤毛/鞭毛障碍的潜在发病机制铺平道路，并为遗传咨询提供补充解释。
