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A novel splicing mutation in helicase for meiosis 1 leads to non-obstructive azoospermia

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

Abstract

Purpose

Non-obstructive azoospermia (NOA) is an essential cause of male infertility for which treatment options are limited. The pathogenic mechanism of NOA, especially idiopathic NOA, remains unclear. Gene variations are associated with the occurrence of NOA. Our study was performed to investigate the genetic causes of NOA.

Methods

Whole exome sequencing (WES) was performed in two probands diagnosed with NOA from a Chinese family. Sanger sequencing was applied to verify the pathogenic variants. A minigene assay was carried out to identify the effect of the splicing variants.

Results

We detected a novel homozygous variant (c.2681-3 T > A) in the HFM1 gene in the two siblings diagnosed with NOA, and their parents carried heterozygous mutations in the same gene. The results of the minigene assay revealed this splicing variant results in exon25 of HFM1 being skipped, leading to a protein truncation (p.Trp894Cysfs*44).

Conclusion

Our results showed that a deleterious splicing variant in HFM1 was related to NOA in these two patients. This novel variant of HFM1 may serve as a potential genetic biomarker for NOA patients.

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Data availability

The authors declare the availability of data upon request.

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Acknowledgements

We would like to thank all the researchers for their contributions.

Funding

This article was funded by the National Natural Science Foundation of China (grant numbers: 82071638; 82001618).

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Author notes

  1. Liangyu Yao, Yifeng Ge, and Tian Du contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Liangyu Yao, Tong Chen & Ninghong Song

  2. Department of Reproductive Medical Center, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China

    Yifeng Ge & Jinzhao Ma

  3. Department of Reproductive Medical Center, Jinling Hospital, Affiliated Hospital of Medical School, Southeast University, Nanjing, 210002, China

    Tian Du

Authors
  1. Liangyu Yao
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  2. Yifeng Ge
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  4. Tong Chen
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  5. Jinzhao Ma
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Contributions

Ninghong Song and Jinzhao Ma designed the project. Liangyu Yao and Yifeng Ge drafted the manuscript. Tian Du participated in the collection of clinical information and revision work. Liangyu Yao carried out the experiments. Ninghong Song and Jinzhao Ma guided the experiment directions and edited the manuscript. All authors read and approved the final manuscript version.

Corresponding authors

Correspondence to Jinzhao Ma or Ninghong Song.

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The authors declare no competing interests.

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Supplementary information

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Supplementary file1 (PDF 49 KB)

10815_2023_2907_MOESM2_ESM.pdf

Supplementary file2 Supplementary Fig. S1: Splicing effect of the c.2681-3T>A variant in HFM1 was scored by varSEAK. (PDF 1194 KB)

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Yao, L., Ge, Y., Du, T. et al. A novel splicing mutation in helicase for meiosis 1 leads to non-obstructive azoospermia. J Assist Reprod Genet 40, 2493–2498 (2023). https://doi.org/10.1007/s10815-023-02907-8

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  • DOI: https://doi.org/10.1007/s10815-023-02907-8

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