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A novel homozygous nonsense variant of STX2 underlies non-obstructive azoospermia in a consanguineous Chinese family

Journal of Human Genetics (2024)Cite this article

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Abstract

Male infertility is a widespread population health concern, causing various degrees of adverse fertility outcomes. We determined the genetic cause of an infertile male from a consanguineous family, expanding the mutant spectrum of male infertility. A non-obstructive azoospermia (NOA) patient was recruited, and histological type of human testicular tissue of the patient categorized as maturation arrest. We identified a novel loss-of-function variant of syntaxin 2 (STX2) (c.142C>T:p.Gln48*) by performing Whole-exome sequencing (WES) on the NOA patient from a consanguineous Chinese family. Sanger sequencing confirmed the p.Gln48* variant was maternally and paternally inherited. The variant was predicted to be deleterious and resulted in aberrant changes to structure and function of STX2 by In silico analysis. In summary, we reported for the first time that a nonsense variant occurred in the exon region of STX2 in an infertile male presenting with NOA, which was beneficial for diagnosis and therapies of NOA.

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In our study, all data and materials are available from the corresponding author on reasonable request.

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Acknowledgements

We thank all participants in the study. This work was supported by Fundamental Research Funds for the Central Institutes (2023GJZD01).

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Author notes

  1. These authors contributed equally: Qi Fang, Lanxi Ran.

Authors and Affiliations

  1. Department of Reproduction, Tianjin First Central Hospital, Tianjin, China

    Qi Fang, Jianyong Di, Ye Liu & Fengqin Xu

  2. Center for Genetics, National Research Institute for Family Planning, Beijing, China

    Lanxi Ran, Xinying Bi & Binbin Wang

  3. Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Lanxi Ran, Xinying Bi & Binbin Wang

  4. NHC Key Laboratory of Reproductive Health Engineering Technology Research (NRIFP), Beijing, China

    Binbin Wang

Authors
  1. Qi Fang
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  2. Lanxi Ran
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  3. Xinying Bi
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  4. Jianyong Di
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  5. Ye Liu
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  6. Fengqin Xu
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Corresponding authors

Correspondence to Fengqin Xu or Binbin Wang.

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The authors declare no competing interests.

Ethics approval and consent to participate

We adhered to the Code of Ethics of the World Medical Association (Declaration of Helsinki, revised in 2013), and the ethical committee of the National Research Institute for Family Planning approved this study. All family members participating in this study signed informed consent.

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Fang, Q., Ran, L., Bi, X. et al. A novel homozygous nonsense variant of STX2 underlies non-obstructive azoospermia in a consanguineous Chinese family. J Hum Genet (2024). https://doi.org/10.1038/s10038-024-01288-9

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  • DOI: https://doi.org/10.1038/s10038-024-01288-9

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