• PMID: 31268247
• Gene Name: EIF4G1
• Condition: Asthenozoospermia
• Association: Associated
• Mutation: c.2521C>T: p.(Pro841Ser) (NC_000003.11: g.184043412C>T) in exon13 and c.2957C>G: p.(Ala986Gly), g.184045117C>G
• Population size: 1
• Population details: 1 case
• Sex: Male
• Infertility type: Male infertility
• Associated genes: NGS

EIF4G1 is a novel candidate gene associated with severe asthenozoospermia

Sha Y, Liu W, Huang X, Li Y, Ji Z, Mei L, Lin S, Kong S, Lu J, Kong L, Zhu X, Lu Z, Ding L.

BACKGROUND: Asthenozoospermia (AZS), also known as asthenospermia, is characterized by reduced motility of ejaculated spermatozoa and is detected in more than 40% of infertile patients. Because the proportion of progressive spermatozoa in severe AZS is <1%, severe AZS is an urgent challenge in reproductive medicine. Several genes have been reported to be relevant to severe asthenospermia. However, these gene mutations are found only in sporadic cases and can explain only a small fraction of severe AZS, so additional genetic pathogenies need to be explored. METHODS AND RESULTS: By screening the variant genes in a patient with severe AZS using whole exome sequencing, we identified biallelic mutations c.2521C>T: p.(Pro841Ser) (NC_000003.11: g.184043412C>T) in exon13 and c.2957C>G: p.(Ala986Gly) (NC_000003.11: g.184045117C>G) in exon17 in the eukaryotic translation initiation factor 4 gamma 1 gene (EIF4G1, RefSeq: NM_004953.4, OMIM: 600495) of the patient. Both of the mutation sites are rare and potentially deleterious. Transmission electron microscopy analysis showed a disrupted axonemal structure with mitochondrial sheath defects. The EIF4G1 protein level was extremely low, and the mitochondrial marker cytochrome c oxidase subunit 4I1 (COXIV, OMIM: 123864) and mitochondrially encoded ATP synthase 6 (ATP6, OMIM: 516060) protein levels were also decreased in the patient's spermatozoa as revealed by WB and IF analysis. This infertility associated with this condition was overcome by intracytoplasmic sperm injections, as his wife became pregnant successfully. CONCLUSION: Our experimental findings indicate that the EIF4G1 gene is a novel candidate gene that may be relevant to severe AZS. CI - © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. FAU - Sha, Yanwei AU - Sha Y AD - Department of Andrology, United Diagnostic and Research Center for Clinical Genetics, School of Public Health & Women and Children's Hospital, Xiamen University, Xiamen, China. FAU - Liu, Wensheng AU - Liu W AD - School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, China. FAU - Huang, Xianjing AU - Huang X AD - Department of Andrology, United Diagnostic and Research Center for Clinical Genetics, School of Public Health & Women and Children's Hospital, Xiamen University, Xiamen, China. FAU - Li, Yang AU - Li Y AD - School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, China. FAU - Ji, Zhiyong AU - Ji Z AD - Department of Andrology, United Diagnostic and Research Center for Clinical Genetics, School of Public Health & Women and Children's Hospital, Xiamen University, Xiamen, China. FAU - Mei, Libin AU - Mei L AD - Department of Andrology, United Diagnostic and Research Center for Clinical Genetics, School of Public Health & Women and Children's Hospital, Xiamen University, Xiamen, China. FAU - Lin, Shaobin AU - Lin S AD - Department of Andrology, United Diagnostic and Research Center for Clinical Genetics, School of Public Health & Women and Children's Hospital, Xiamen University, 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 - Kong, Lingyuan AU - Kong L AD - Department of Andrology, United Diagnostic and Research Center for Clinical Genetics, School of Public Health & Women and Children's Hospital, Xiamen University, Xiamen, China. FAU - Zhu, Xingshen AU - Zhu X AD - School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, China. FAU - Lu, Zhongxian AU - Lu Z AUID- ORCID: 0000-0002-1682-7147 AD - School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, China. AD - Fujian Provincial Key Laboratory of Reproductive Health Research, Medical College of Xiamen University, Xiamen, China.