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A novel variant in CFAP69 causes asthenoteratozoospermia with treatable ART outcomes and a literature review

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Multiple morphological abnormalities of the sperm flagella (MMAF) are a severe form of sperm defect causing male infertility. Previous studies identified the variants in the CFAP69 gene as a MMAF-associated factor, but few cases have been reported. This study was performed to identify additional variants in CFAP69 and describe the semen characteristics and outcomes of assisted reproductive technology (ART) in CFAP69-affected couples.

Methods

Genetic testing with next-generation sequencing (NGS) panel of 22 MMAF-associated genes and Sanger sequencing was performed in a cohort of 35 infertile males with MMAF to identify pathogenic variants. Morphological, ultrastructural, and immunostaining analyses were performed to investigate the characteristics of probands’ spermatozoa. ART with intracytoplasmic sperm injection (ICSI) was carried out for the affected couples to get their own progenies.

Results

We identified a novel frameshift variant in CFAP69 (c.2061dup, p. Pro688Thrfs*5) from a MMAF-affected infertile male with low sperm motility and malformed morphology of sperm. Furthermore, transmission electron microscopy and immunofluorescence staining revealed that the variant induced the aberrant ultrastructure and reduction of CFAP69 expression in the proband’s spermatozoa. Moreover, the partner of the proband birthed a healthy girl through ICSI.

Conclusions

This study expanded the variant spectrum of CFAP69 and described the good outcome of ART treatment with ICSI, which is beneficial to the molecular diagnosis, genetic counseling, and treatment of infertile males with MMAF in the future.

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Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Acknowledgements

We thank Li Wang and Dandan Song in the Center of Cryo-Electron Microscopy (CCEM), Zhejiang University, for their technical support.

Funding

This work was supported by the Chongqing medical scientific research project (joint project of Chongqing Health Commission and Science and Technology Bureau, 2023MSXM008) and Open Project Fund from the National Health Commission Key Laboratory of Male Reproductive Health/National Research Institute for Family Planning (2022GJP0101).

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Authors and Affiliations

  1. Center for Reproductive Medicine, Women and Children’s Hospital of Chongqing Medical University, Chongqing, 400013, China

    Xiangrong Tang, Jing Ma, Xinglin Wang, Shunhua Long, Haibing Yu, Guoning Huang & Tingting Lin

  2. Chongqing Health Center for Women and Children, Chongqing, 400013, China

    Xiangrong Tang, Jing Ma, Xinglin Wang, Shunhua Long, Haibing Yu, Guoning Huang & Tingting Lin

  3. Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, 400020, China

    Ling Wan & Jigao Yang

Authors
  1. Xiangrong Tang
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  2. Jing Ma
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  3. Xinglin Wang
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  4. Shunhua Long
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  5. Ling Wan
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  8. Guoning Huang
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  9. Tingting Lin
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Contributions

Tingting Lin, Guoning Huang, and Xiangrong Tang conceived and designed the study and drafted the manuscript. Jing Ma, Shunhua Long, Xiangrong Tang, and Ling Wan carried out the genetic studies and the immunoassays. Haibing Yu provided the clinical samples. Xinglin Wang conducted the ART cycle. Tingting Lin, Guoning Huang, and Jigao Yang critically commented on and edited the manuscript. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Guoning Huang or Tingting Lin.

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Ethics approval

This study was approved by the Clinical Application and Ethics Committee of Human Assisted Reproductive Technology of Chongqing Health Center for Women and Children (2022-RGI-05).

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The authors declare no competing interests.

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Tang, X., Ma, J., Wang, X. et al. A novel variant in CFAP69 causes asthenoteratozoospermia with treatable ART outcomes and a literature review. J Assist Reprod Genet 40, 2175–2184 (2023). https://doi.org/10.1007/s10815-023-02873-1

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