• PMID: 31658987
• Gene Name: DNAH17
• Condition: Flagella destabilization and asthenozoospermia
• Association: Associated
• Mutation: c.G5408A, p.C1803Y
• Population size: 1
• Population details: 1 case
• Sex: Male
• Infertility type: Male infertility
• Associated genes: NGS

A DNAH17 missense variant causes flagella destabilization and asthenozoospermia

Zhang B, Ma H, Khan T, Ma A, Li T, Zhang H, Gao J, Zhou J, Li Y, Yu C, Bao J, Ali A, Murtaza G, Yin H, Gao Q, Jiang X, Zhang F, Liu C, Khan I, Zubair M, Hussain HMJ, Khan R, Yousaf A, Yuan L, Lu Y, Xu X, Wang Y, Tao Q, Hao Q, Fang H, Cheng H, Zhang Y, Shi Q.

Asthenozoospermia is a common cause of male infertility, but its etiology remains incompletely understood. We recruited three Pakistani infertile brothers, born to first-cousin parents, displaying idiopathic asthenozoospermia but no ciliary-related symptoms. Whole-exome sequencing identified a missense variant (c.G5408A, p.C1803Y) in DNAH17, a functionally uncharacterized gene, recessively cosegregating with asthenozoospermia in the family. DNAH17, specifically expressed in testes, was localized to sperm flagella, and the mutation did not alter its localization. However, spermatozoa of all three patients showed higher frequencies of microtubule doublet(s) 4-7 missing at principal piece and end piece than in controls. Mice carrying a homozygous mutation (Dnah17M/M) equivalent to that in patients recapitulated the defects in patients' sperm tails. Further examinations revealed that the doublets 4-7 were destabilized largely due to the storage of sperm in epididymis. Altogether, we first report that a homozygous DNAH17 missense variant specifically induces doublets 4-7 destabilization and consequently causes asthenozoospermia, providing a novel marker for genetic counseling and diagnosis of male infertility. CI - © 2019 Zhang et al. FAU - Zhang, Beibei AU - Zhang B AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Ma, Hui AU - Ma H AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Khan, Teka AU - Khan T AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Ma, Ao AU - Ma A AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Li, Tao AU - Li T AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Zhang, Huan AU - Zhang H AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Gao, Jianing AU - Gao J AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Zhou, Jianteng AU - Zhou J AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Li, Yang AU - Li Y AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Yu, Changping AU - Yu C AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Bao, Jianqiang AU - Bao J AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Ali, Asim AU - Ali A AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Murtaza, Ghulam AU - Murtaza G AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Yin, Hao AU - Yin H AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Gao, Qian AU - Gao Q AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Jiang, Xiaohua AU - Jiang X AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Zhang, Feng AU - Zhang F AD - Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering at School of Life Sciences, Institute of Reproduction and Development, Fudan University, Shanghai, China. AD - Key Laboratory of Reproduction Regulation of National Population and Family Planning Commission, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai, China. AD - Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China. FAU - Liu, Chunyu AU - Liu C AD - Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering at School of Life Sciences, Institute of Reproduction and Development, Fudan University, Shanghai, China. FAU - Khan, Ihsan AU - Khan I AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Zubair, Muhammad AU - Zubair M AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Hussain, Hafiz Muhammad Jafar AU - Hussain HMJ AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Khan, Ranjha AU - Khan R AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Yousaf, Ayesha AU - Yousaf A AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Yuan, Limin AU - Yuan L AD - Analysis and test center, Co-Innovation Center for Modern Production Technology of Grain Crops, Yangzhou University, Yangzhou, China. FAU - Lu, Yan AU - Lu Y AD - Analysis and test center, Co-Innovation Center for Modern Production Technology of Grain Crops, Yangzhou University, Yangzhou, China. FAU - Xu, Xiaoling AU - Xu X AD - Department of Respiration, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. FAU - Wang, Yun AU - Wang Y AD - Department of Respiration, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. FAU - Tao, Qizhao AU - Tao Q AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Hao, Qiaomei AU - Hao Q AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Fang, Hui AU - Fang H AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Cheng, Hongtao AU - Cheng H AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China. FAU - Zhang, Yuanwei AU - Zhang Y AD - The First Affiliated Hospital of University of Science and Technology of China, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China-Shenyang Jinghua Hospital Joint Center for Human Reproduction and Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei, China.