A novel loss-of-function SYCP2 variant causes asthenoteratozoospermia in infertile males
Background:Infertility is a multiplex disorder in the reproductive system. Unexplained infertility affects 2%-3% of reproductive-aged couples. Male factors contribute to about half of all infertility cases. About 15% of these cases are predicted to have a genetic etiology. With the wide application...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1595720/full |
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| author | Cong Liu Cong Liu Cong Liu Yinfeng Zhang Yinfeng Zhang Yinfeng Zhang Youming Zhao Youming Zhao Youming Zhao Haining Luo Haining Luo Haining Luo |
| author_facet | Cong Liu Cong Liu Cong Liu Yinfeng Zhang Yinfeng Zhang Yinfeng Zhang Youming Zhao Youming Zhao Youming Zhao Haining Luo Haining Luo Haining Luo |
| author_sort | Cong Liu |
| collection | DOAJ |
| description | Background:Infertility is a multiplex disorder in the reproductive system. Unexplained infertility affects 2%-3% of reproductive-aged couples. Male factors contribute to about half of all infertility cases. About 15% of these cases are predicted to have a genetic etiology. With the wide application of whole exome sequencing (WES), more and more variations in male infertility have been identified.Methods:A patient diagnosed with asthenoteratozoospermia was involved in this study. WES was performed in the patient, and Sanger sequencing was used to confirm the variation. Mini-gene splicing assays were performed to validate the effect on the alternative splicing of the variation.Results:A novel heterozygous splice variant was identified in SYCP2 (c.2600+ 5G>C) in the patient ,which inherited from his phenotypically normal mother. SYCP2 encodes a protein critical for the synapsis of homologous chromosomes during meiosis I, and its disruption can impair spermatogenesis. Mini-gene splicing assays confirmed that this splicing variant impacted alternative splicing and that the stop codon appeared early, which was very likely to result in the loss of function of the protein and lead to the occurrence of male infertility.Conclusion:Our results suggested that the c.2600+5G>C variation in SYCP2 might be the genetic etiology for male infertility in this pedigree. This finding expanded the known genotype spectrum of male infertility and provided new etiological information for male infertility. |
| format | Article |
| id | doaj-art-388673238aaf43a59f5fbb71ec24e437 |
| institution | DOAJ |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-388673238aaf43a59f5fbb71ec24e4372025-08-20T02:57:29ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-05-011610.3389/fgene.2025.15957201595720A novel loss-of-function SYCP2 variant causes asthenoteratozoospermia in infertile malesCong Liu0Cong Liu1Cong Liu2Yinfeng Zhang3Yinfeng Zhang4Yinfeng Zhang5Youming Zhao6Youming Zhao7Youming Zhao8Haining Luo9Haining Luo10Haining Luo11Department of Center for Reproductive Medicine, Tianjin Central Hospital of Gynaecology Obsterics, Tianjin, ChinaTianjin Institute of Gynaecology Obsteric, Tianjin Central Hospital of Gynaecology Obsterics, Tianjin, ChinaTianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynaecology Obsterics, Tianjin, ChinaDepartment of Center for Reproductive Medicine, Tianjin Central Hospital of Gynaecology Obsterics, Tianjin, ChinaTianjin Institute of Gynaecology Obsteric, Tianjin Central Hospital of Gynaecology Obsterics, Tianjin, ChinaTianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynaecology Obsterics, Tianjin, ChinaDepartment of Center for Reproductive Medicine, Tianjin Central Hospital of Gynaecology Obsterics, Tianjin, ChinaTianjin Institute of Gynaecology Obsteric, Tianjin Central Hospital of Gynaecology Obsterics, Tianjin, ChinaTianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynaecology Obsterics, Tianjin, ChinaDepartment of Center for Reproductive Medicine, Tianjin Central Hospital of Gynaecology Obsterics, Tianjin, ChinaTianjin Institute of Gynaecology Obsteric, Tianjin Central Hospital of Gynaecology Obsterics, Tianjin, ChinaTianjin Key Laboratory of Human Development and Reproductive Regulation, Tianjin Central Hospital of Gynaecology Obsterics, Tianjin, ChinaBackground:Infertility is a multiplex disorder in the reproductive system. Unexplained infertility affects 2%-3% of reproductive-aged couples. Male factors contribute to about half of all infertility cases. About 15% of these cases are predicted to have a genetic etiology. With the wide application of whole exome sequencing (WES), more and more variations in male infertility have been identified.Methods:A patient diagnosed with asthenoteratozoospermia was involved in this study. WES was performed in the patient, and Sanger sequencing was used to confirm the variation. Mini-gene splicing assays were performed to validate the effect on the alternative splicing of the variation.Results:A novel heterozygous splice variant was identified in SYCP2 (c.2600+ 5G>C) in the patient ,which inherited from his phenotypically normal mother. SYCP2 encodes a protein critical for the synapsis of homologous chromosomes during meiosis I, and its disruption can impair spermatogenesis. Mini-gene splicing assays confirmed that this splicing variant impacted alternative splicing and that the stop codon appeared early, which was very likely to result in the loss of function of the protein and lead to the occurrence of male infertility.Conclusion:Our results suggested that the c.2600+5G>C variation in SYCP2 might be the genetic etiology for male infertility in this pedigree. This finding expanded the known genotype spectrum of male infertility and provided new etiological information for male infertility.https://www.frontiersin.org/articles/10.3389/fgene.2025.1595720/fullmale infertilitywhole exome sequenceSYCP2gene variationmini-gene splicing assay |
| spellingShingle | Cong Liu Cong Liu Cong Liu Yinfeng Zhang Yinfeng Zhang Yinfeng Zhang Youming Zhao Youming Zhao Youming Zhao Haining Luo Haining Luo Haining Luo A novel loss-of-function SYCP2 variant causes asthenoteratozoospermia in infertile males Frontiers in Genetics male infertility whole exome sequence SYCP2 gene variation mini-gene splicing assay |
| title | A novel loss-of-function SYCP2 variant causes asthenoteratozoospermia in infertile males |
| title_full | A novel loss-of-function SYCP2 variant causes asthenoteratozoospermia in infertile males |
| title_fullStr | A novel loss-of-function SYCP2 variant causes asthenoteratozoospermia in infertile males |
| title_full_unstemmed | A novel loss-of-function SYCP2 variant causes asthenoteratozoospermia in infertile males |
| title_short | A novel loss-of-function SYCP2 variant causes asthenoteratozoospermia in infertile males |
| title_sort | novel loss of function sycp2 variant causes asthenoteratozoospermia in infertile males |
| topic | male infertility whole exome sequence SYCP2 gene variation mini-gene splicing assay |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1595720/full |
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