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Deleterious variant in FAM71D cause male infertility with asthenoteratospermia

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Abstract

Asthenoteratospermia is a significant cause of male infertility. FAM71D (Family with sequence similarity 71, member D), as a novel protein exclusively expressed in the testis, has been found to be associated with sperm motility. However, the association of FAM71D mutation with male infertility has yet to be examined. Here, we conducted whole-exome sequencing and identified a homozygous missense mutation c.440G > A (p. Arg147Gln) of FAM71D in an asthenoteratospermia-affected man from a consanguineous family. The FAM71D variant is extremely rare in human population genome databases and predicted to be deleterious by multiple bioinformatics tools. Semen analysis indicated decreased sperm motility and obvious morphological abnormalities in sperm cells from the FAM71D-deficient man. Immunofluorescence assays revealed that the identified FAM71D mutation had an important influence on the assembly of sperm structure-related proteins. Furthermore, intra-cytoplasmic sperm injection (ICSI) treatment performed on the infertile man with FAM71D variant achieved a satisfactory outcome. Overall, our study identified FAM71D as a novel causative gene for male infertility with asthenoteratospermia, for which ICSI treatment may be suggested to acquire good prognosis. All these findings will provide effective guidance for genetic counselling and assisted reproduction treatments of asthenoteratospermia-affected subjects.

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Acknowledgements

We would like to sincerely thank the patient and his parents for their support and participation. We also thank the Center of Cryo-Electron Microscopy at Zhejiang University for technical support.

Funding

This study was supported by the National Key Research and Development Program of China (2021YFC2701400), the National Natural Science Foundation of China (31625015, 32100480, 32370654, 32200485, 82171586); the State Key Laboratory of Reproductive Medicine (SKLRM-K202002) and the China Postdoctoral Science Foundation (2020TQ0072).

Author information

Author notes

  1. Xiaobin Zhu, Liu Liu and Shixiong Tian contributed equally to this work.

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Reproductive Medical Center, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Xiaobin Zhu, Qian Chen & Aijun Zhang

  2. Obstetrics and Gynecology Hospital, Institute of Medical Genetics and Genomics, Fudan University, Shanghai, 200011, China

    Liu Liu & Shuyan Tang

  3. Department of Computational Biology, School of Life Science, Fudan University, Shanghai, 200438, China

    Liu Liu

  4. Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 200438, China

    Shixiong Tian & Shuyan Tang

  5. Shanghai Institute of Medical Genetics, Shanghai Children’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200040, China

    Guijun Zhao

  6. Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200940, China

    Erlei Zhi

  7. International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China

    Feng Zhang & Chunyu Liu

Authors
  1. Xiaobin Zhu
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  2. Liu Liu
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Contributions

CL, ST and AZ designed this study and revised the Manuscript. Feng Zhang contributed to the discussion of the data. XZ and LL recruited the samples and wrote the manuscript. ST performed clinical phenotyping and the immunofluorescence analyses. LL, GZ, EZ and QC conducted the whole-exome sequencing and performed the bioinformatic analyses. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Aijun Zhang, Shuyan Tang or Chunyu Liu.

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Competing interests

The authors declare that they have no conflict of interest.

Ethics approval

The study was approved by the Ethics Committee of Human Sperm Bank of Fudan University (Shanghai, China). Informed consent was obtained from all of the individuals included in this study.

Additional information

Communicated by Shuhua Xu.

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Zhu, X., Liu, L., Tian, S. et al. Deleterious variant in FAM71D cause male infertility with asthenoteratospermia. Mol Genet Genomics 299, 35 (2024). https://doi.org/10.1007/s00438-024-02117-6

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