Abstract
Acephalic spermatozoa syndrome (ASS) is a severe form of teratozoospermia, previous studies have shown that SUN5 mutations are the major cause of acephalic spermatozoa syndrome. This study is to identify the pathogenic mutations in SUN5 leading to ASS. PCR and Sanger sequence were performed to define the breakpoints and mutations in SUN5. Whole genome sequencing (WGS) was performed to detect heterozygous deletion. Western blotting and immunofluorescence analysis detected the expression level and localization of SUN5. Furthermore, the pathogenicity of the mutant SUN5 was predicted in silico and was verified by the experiments in vitro. We identified one novel homozygous missense mutation (c.775G>A; p.G259S) and one compound heterozygous including one reported missense mutation (c.1043A>T; p.N348I) and a large deletion that contains partial EFCAB8 (NM_001143967.1) and BPIFB2 (NM_025227) and complete SUN5 (NM_080675), and one recurrent homozygous splice-site mutation (c.340G>A; p.G114R) in SUN5 in three patients with ASS. Our results showed that SUN5 could not be detected in the patients’ spermatozoa and the exogenous expression level of the mutant protein was decreased in transfected HEK-293T cells. This study expands the mutational spectrum of SUN5. We recommended a clinical diagnostic strategy for SUN5 genomic deletion to screen heterozygous deletions and indicated that the diagnostic value of screening for SUN5 mutations and deletions in infertile men with ASS.
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Data and materials are available on request from the corresponding author.
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Acknowledgements
We would like to sincerely thank the patients and their families for their participation.
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This study is funded by the National Natural Science Foundation of China, Grand/Award number: 82071701, 81972641; Natural Science Foundation of Anhui Province, Grand/Award number: 1908085J28; Key R&D program of Anhui Province, Grand/Award number: 201904a07020050; the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences, Grand/Award number: 2019PT310002; Scientific Research Foundation of the Institute for Translational Medicine of Anhui Province, Grand/Award number: SRFITMAP 2017zhyx29, ZHYX2020A00.
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F.Z., Y.C. and F.W. conceived and designed the experiments. M.L., J.Z., Z.D. and X.Z. collected the samples. M.X., Y.W., K.W. and S.K. performed the experiments. M.X., Y.W., K.W., S.K., X.S., F.W., Y.C. and F.Z. analyzed the data. M.X. wrote the article. All authors approved the final article.
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Xiang, M., Wang, Y., Wang, K. et al. Novel Mutation and Deletion in SUN5 Cause Male Infertility with Acephalic Spermatozoa Syndrome. Reprod. Sci. 29, 646–651 (2022). https://doi.org/10.1007/s43032-021-00665-5
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DOI: https://doi.org/10.1007/s43032-021-00665-5