CCDC9 is identified as a novel candidate gene of severe asthenozoospermia

ABSTRACT

Owing to less than 1% of motile spermatozoa in the ejaculated semen, severe asthenozoospermia is a serious threat to the male reproductive health. Herein, we identified a novel homozygous variant in CCDC9 (NC_000019.9: g.47763960C>T, NM_015603.3, NP_056418.1: p. Ser109Leu) in a patient from a consanguineous family. The variant was highly pathogenic and was predicted to be a candidate gene for asthenozoospermia through in silico analysis. The CCDC9 protein levels were significantly low and its morphology and ultrastructure were severely damaged in the spermatozoa containing the novel variant. Therefore, CCDC9 may be a novel pathogenic gene associated with severe asthenozoospermia.

Abbreviations: CCDC9: coiled-coil domain containing 9; AZS: asthenozoospermia; MP: midpiece; MS: mitochondrial sheath; ODF: outer dense fiber; CP: central pair; DMT: doublet microtubule; IDA: inner dynein arm; ODA: outer dynein arm.

KEYWORDS:

• Severe asthenozoospermia
• homozygous variant
• whole exome sequencing
• CCDC9

Acknowledgments

The authors would like to sincerely thank the patient and his family for their interest and cooperation.

Disclosure statement

No potential conflict of interest was reported by the authors.

Authors contributions

Designed the study and revised the manuscript: PQ, JC, XW; Analyzed the data: YS, YX; Performed experiments and wrote the manuscript: XW, WL; Collected and analyzed the data: LM, SL, ZJ; Assisted with manuscript writing: XW, ZS. All authors have reviewed and approved the final version of the manuscript.

Supplementary Material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the following grants: The open project of Key Laboratory of Male Reproduction and Genetics, National Health and Family Planning Commission [Grant No. KF201704]; Natural Science Foundation of Shandong Province [Grant No. ZR2017LH012]; the National Natural Science Foundation of China [Grant No. 81871200]; the Science Technology Guidance Project of Fujian Province [Grant No. 2017D018].