• PMID: 30811583
• Gene Name: DNAH2
• Condition: Multiple morphological abnormalities of flagella (MMAF), Teratozoospermia
• Association: Associated
• Mutation: c.9298C>T p.R3100W, c.5770C>T p.R1924C, c.11500C>T p.R3834X, c.6960C>A p.S2320R, c.11503T>C p.S3835P
• Population size: 3
• Population details: 3 cases
• Sex: Male
• Infertility type: Male infertility
• Associated genes: NGS

DNAH2 is a novel candidate gene associated with multiple morphological abnormalities of the sperm flagella

Li Y, Sha Y, Wang X, Ding L, Liu W, Ji Z, Mei L, Huang X, Lin S, Kong S, Lu J, Qin W, Zhang X, Zhuang J, Tang Y, Lu Z.

Multiple morphological abnormalities of flagella (MMAF) is one kind of severe teratozoospermia. Gene mutations reported in previous works only revealed the pathogenesis of approximately half of the MMAF cases, and more genetic defects in MMAF need to be explored. In the present study, we performed a genetic analysis on Han Chinese men with MMAF using whole-exome sequencing. After filtering out the cases with known gene mutations, we identified five novel mutation sites in the DNAH2 gene in three cases from three families. These mutations were validated through Sanger sequencing and absent in all control individuals. In silico analysis revealed that these DNAH2 variations are deleterious. The spermatozoa with DNAH2 mutations showed severely disarranged axonemal structures with mitochondrial sheath defection. The DNAH2 protein level was significantly decreased and inner dynein arms were absent in the spermatozoa of patients. ICSI treatment was performed for two MMAF patients with DNAH2 mutations and the associated couples successfully achieved pregnancy, indicating good nuclear quality of the sperm from the DNAH2 mutant patients. Together, these data suggest that the DNAH2 mutation can cause severe sperm flagella defects that damage sperm motility. These results provide a novel genetic pathogeny for the human MMAF phenotype. CI - © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Li, Yang AU - Li Y AD - State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China. FAU - Sha, Yanwei AU - Sha Y AD - Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, China. FAU - Wang, Xiong AU - Wang X AD - Reproductive Medicine Center, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Qingdao, China. FAU - Ding, Lu AU - Ding L AD - Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, China. FAU - Liu, Wensheng AU - Liu W AD - State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China. FAU - Ji, Zhiyong AU - Ji Z AD - Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, China. FAU - Mei, Libin AU - Mei L AD - Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, China. FAU - Huang, Xianjing AU - Huang X AD - Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, China. FAU - Lin, Shaobin AU - Lin S AD - Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, China. FAU - Kong, Shuangbo AU - Kong S AD - Fujian Provincial Key Laboratory of Reproductive Health Research, Medical College of Xiamen University, Xiamen, China. FAU - Lu, Jinhua AU - Lu J AD - Fujian Provincial Key Laboratory of Reproductive Health Research, Medical College of Xiamen University, Xiamen, China. FAU - Qin, Weibing AU - Qin W AD - Key Laboratory of Male Reproduction and Genetics, National Health and Family Planning Commission, Guangzhou, China. FAU - Zhang, Xinzhong AU - Zhang X AD - Key Laboratory of Male Reproduction and Genetics, National Health and Family Planning Commission, Guangzhou, China. FAU - Zhuang, Jianmin AU - Zhuang J AD - Reproductive Medicine Center, Xiamen Haicang Hospital, Xiamen, China. FAU - Tang, Yunge AU - Tang Y AD - Key Laboratory of Male Reproduction and Genetics, National Health and Family Planning Commission, Guangzhou, China.