Abstract
The cell division cycle 20 (CDC20) protein is a co-activator of anaphase-promoting complex/cyclosome (APC/C), required for mitotic exit and also meiotic exit, containing seven WD40 repeats in the C-terminus responsible for protein-protein interactions. Recently, a previous study has shown that biallelic mutations in CDC20 are causative for female infertility with abnormalities in oocyte maturation and embryonic development. This study is to further identify new mutations of CDC20 and the prevalence of variants in our cohort. A cohort of 50 primary infertile females with oocyte maturation abnormality and early embryonic arrest were recruited. Genomic DNA was isolated from peripheral blood samples. Mutation screening of all the coding regions of CDC20 was performed by Sanger sequencing. The pathogenicity of the identified variants on the CDC20 protein was accessed in silico. Two CDC20 variants, a nonsense mutation p.R262* and a missense mutation p.A211T, identified in one female of 50 unrelated affected individuals, accounting for a relative small proportion of this cohort (2%). In silico analysis revealed that the p.R262* would cause no production of protein or a truncated protein lacking five WD40 repeats in the C-terminus; and that p.A211T may interfere with the formation of a deep hydrophobic pocket and thus disturb the binding of CDC20 protein to the substrates of APC/C. This study identified two novel mutations in CDC20, further expanding the mutation spectrum of this gene. Our findings further confirm that biallelic mutations in CDC20 occur in a proportion of infertile females with oocyte maturation abnormality and early embryonic arrest.
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Data and materials are available from the corresponding author on reasonable request.
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We thank all families for participating in this study.
Funding
This study was supported by the National Natural Science Foundation of China (81801440 to L.H.), the Natural Science Foundation of Anhui Province (1808085MH241 to L.H.), the Fundamental Research Funds for the Central Universities (WK9110000028 to L.H.), and the National Key R&D Program of China (2018YFC1003900 to X.T.).
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L.H. and X.T. conceived and designed the experiments. L.H., F.L., J.J., L.L., and X.T. collected the samples. L.H., F.W., S.K., and Y.W. performed the experiments. L.H., G.S., and X.T. analyzed the data. L.H. wrote the paper. All authors approved the final manuscript.
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The study protocol and all subjects who participated in this study were approved by biomedical research ethics committee of Anhui Medical University in which informed consent was obtained from all subjects prior to participation.
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Huang, L., Wang, F., Kong, S. et al. Novel Mutations in CDC20 Are Associated with Female Infertility Due to Oocyte Maturation Abnormality and Early Embryonic Arrest. Reprod. Sci. 28, 1930–1938 (2021). https://doi.org/10.1007/s43032-021-00524-3
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DOI: https://doi.org/10.1007/s43032-021-00524-3