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The second mutation of SYCE1 gene associated with autosomal recessive nonobstructive azoospermia

  • Genetics
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Abstract

Purpose

It is estimated that 40–50% of infertility among human couples is due to male infertility. Azoospermia is estimated to occur in 1% of all men and to be the cause of 10–20% of male infertility. Genetic defects, including single gene effects, maybe cause of azoospermia in 20–30% of affected males. Here, we aim to identify the genetic cause of azoospermia in a man who is also affected by hereditary spastic paraplegia.

Methods

The proband was subjected to whole-exome sequencing, followed by a comprehensive in silico analysis to identify the azoospermia causative gene.

Results

A novel splice site mutation c.375-2A > G in SYCE1 that is thought to be the cause of azoospermia was identified. This variant co-segregated with azoospermia status in the family that has three additional affected males.

Conclusion

SYCE1 gene encodes synaptonemal complex (SC) central element 1 protein which contributes to the formation of the synaptonemal complex during meiosis. Syce1 null male and female mice have been shown to be infertile. There have only been two reports on the effects of SYCE1 mutations in humans; it was shown as the cause of primary ovarian failure (POI) in one and as the cause of nonobstructive azoospermia (NOA) in another. We suggest that the mutation 375-2A > G, which affects the acceptor splice site within intron 6 of SYCE1, is the likely cause of azoospermia and subsequent infertility in the family studied. The finding constitutes the third report of SYCE1mutations that affect infertility in humans and further supports its contribution to this condition.

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Acknowledgments

We acknowledge the Iran National Institute for Medical Research Development (NIMAD; grant number 963846) and the University of Social Welfare and Rehabilitation Sciences for funding the research and thank the patients and their family members for participating in the study.

Funding

National Institute for Medical Research Development (NIMAD) and the University of Social Welfare and Rehabilitation Sciences.

Author information

Authors and Affiliations

  1. Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran

    Mahdieh Pashaei, Mohammad Masoud Rahimi Bidgoli, Davood Zare-Abdollahi, Hossein Najmabadi & Afagh Alavi

  2. Department of Radiation Oncology, Winship Cancer Institute of Emory University, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Ramona Haji-Seyed-Javadi

  3. Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Farzad Fatehi

Authors
  1. Mahdieh Pashaei
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  2. Mohammad Masoud Rahimi Bidgoli
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  4. Hossein Najmabadi
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Contributions

Mahdieh Pashaei: tertiary analysis of exome sequencing data and contributed to writing of manuscript

Mohammad Masoud Rahimi Bidgoli: analysis of exome sequencing data, mutation screening of SYCE1 in azoospermic proband, segregation analysis pertaining to azoospermia, and amplification of cDNA in order to analysis of splice site variant

Farzad Fatehi: clinical evaluations and editing of manuscript

Davood Zare-Abdollahi: karyotyping, RNA extraction, cDNA synthesis, and editing of manuscript

Hossein Najmabadi: advisor of MP

Ramona Haji-Seyed-Javadi: primary analysis of exome sequencing data

Afagh Alavi: designed and supervised the research and wrote the manuscript

Corresponding authors

Correspondence to Farzad Fatehi or Afagh Alavi.

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Conflict of interest

All authors claim the absence of financial interests and the absence of conflicts of interest.

Ethical standards

All participants, after being informed of the nature of the research, consented to participate to the study. This research was performed in accordance with the Declaration of Helsinki and with the approval of the ethics board of the University of Social Welfare and Rehabilitation Sciences.

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Figure S1

Filtering steps of variants obtained from the whole exome sequencing of AZO-III13. MAF, minor allele frequency. (PNG 756 kb).

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Figure S2

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Pashaei, M., Rahimi Bidgoli, M.M., Zare-Abdollahi, D. et al. The second mutation of SYCE1 gene associated with autosomal recessive nonobstructive azoospermia. J Assist Reprod Genet 37, 451–458 (2020). https://doi.org/10.1007/s10815-019-01660-1

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  • DOI: https://doi.org/10.1007/s10815-019-01660-1

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