- Article
- Published:
- Jiao Qin1,2,
- Jinyu Wang3,
- Jianhai Chen4,
- Jinyan Xu1,2,
- Shanling Liu3,
- Dong Deng5 &
- …
- Fuping Li1,2
Journal of Human Genetics (2024)Cite this article
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- Diseases
- Mutation
Abstract
Human infertility affects 10–15% of couples. Asthenozoospermia accounts for 18% of men with infertility and is a common male infertility phenotype. The nexin-dynein regulatory complex (N-DRC) is a large protein complex in the sperm flagellum that connects adjacent doublets of microtubules. Defects in the N-DRC can disrupt cilia/flagellum movement, resulting in primary ciliary dyskinesia and male infertility. Using whole-exome sequencing, we identified a pathological hom*ozygous variant of the dynein regulatory complex subunit 3 (DRC3) gene, which expresses leucine-rich repeat-containing protein 48, a component of the N-DRC, in a patient with asthenozoospermia. The variant ENST00000313838.12: c.644dup (p. Glu216GlyfsTer36) causes premature translational arrest of DRC3, resulting in a dysfunctional DRC3 protein. The patient’s sem*n count, color, and pH were normal according to the reference values of the World Health Organization guidelines; however, sperm motility and progressive motility were reduced. DRC3 protein was not detected in the patient’s sperm and the ultrastructure of the patient’s sperm flagella was destroyed. More importantly, the DRC3 variant reduced its interaction with other components of the N-DRC, including dynein regulatory complex subunits 1, 2, 4, 5, 7, and 8. Our data not only revealed the essential biological functions of DRC3 in sperm flagellum movement and structure but also provided a new basis for the clinical genetic diagnosis of male infertility.
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Acknowledgements
We wish to thank the patient and medical staff of Department of Andrology/Sichuan Human Sperm Bank, West China Second University Hospital.
Funding
This study was supported by the Clinical Discipline Development Fund, West China Second University Hospital of China (KL061).
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Authors and Affiliations
Department of Andrology/Sichuan Human Sperm Bank, West China Second University Hospital, Sichuan University, Chengdu, China
Jiao Qin,Jinyan Xu&Fuping Li
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
Jiao Qin,Jinyan Xu&Fuping Li
Department of Medical Genetics, West China Second University Hospital of Sichuan University, Chengdu, 610041, China
Jinyu Wang&Shanling Liu
Department of Ecology and Evolution, Biological Sciences Division, The University of Chicago, 1101 E 57th Street, Chicago, IL, 60637, USA
Jianhai Chen
Department of Obstetrics, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, 610041, China
Dong Deng
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Contributions
Jiao Qin designed the study and wrote the paper. Jinyu Wang performed the experiments and analyzed the data. Jianhai Chen analyzed the sequencing data and identified the variant gene. Jinyan Xu collected clinical samples and signed informed consent with human subjects, Fuping Li, Dong Deng and Shanling Liu directed this study.
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Correspondence to Shanling Liu, Dong Deng or Fuping Li.
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The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.
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The study was reviewed and approved by Review Board of the West China Second University Hospital in China, Number 2020-102. All human subjects provided informed consent for this study.
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Qin, J., Wang, J., Chen, J. et al. hom*ozygous variant in DRC3 (LRRC48) gene causes asthenozoospermia and male infertility. J Hum Genet (2024). https://doi.org/10.1038/s10038-024-01253-6
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DOI: https://doi.org/10.1038/s10038-024-01253-6
