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Deleterious mutation in SYCE1 is associated with non-obstructive azoospermia

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

Abstract

Purpose

To determine the molecular basis of familial, autosomal-recessive, non-obstructive azoospermia in a consanguineous Iranian Jewish family.

Methods

We investigated the genetic cause of non-obstructive azoospermia in two affected siblings from a consanguineous family. Homozygosity mapping in the DNA samples of the patients and their normospermic brother was followed by exome analysis of one of the patients. Other family members were genotyped for the mutation by Sanger sequencing. The mutation effect was demonstrated by immunostaining of the patients’ testicular tissue.

Results

The two patients were homozygous for a splice site mutation in SYCE1 which resulted in retention of intron three in the cDNA and premature stop codon. SYCE1 encodes a Synaptonemal Complex protein which plays an essential role during meiosis. Immunostaining of patient’s testicular tissue with anti-Syce1 antibody revealed an undetectable level of Syce1. Histological examination of the patients’ tissue disclosed immature-stages spermatocytes without mature forms, indicating maturation arrest.

Conclusion

The significance of most synaptonemal complex proteins was previously demonstrated in a mutant mouse model. The present report underscores the importance of synaptonemal complex proteins in spermatogenenesis in humans. Our new approach, combining homozygosity mapping and exome sequencing, resulted in one of the first reports of an autosomal-recessive form of NOA.

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Acknowledgment

We wish to thank Vivi Zuri Naama Lexner and Olga Genin for excellent technical assistance.

Conflict of interest

The authors have no conflict of interest to declare.

Contributor statement

YC, BY, AS, HG, SZ, CR, OE and AF conceived and designed the experiments; EMS, YC, BY, AS, HG, and SZ performed the experiments; all the coauthors analyzed the data and participated in the writing of the paper; EMS undertook patient management, collection of samples, and delineation of the phenotype. The research was supported in part by a grant from the Joint Research Fund of the Hebrew University and Hadassah.

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Author notes

  1. Yuval Cinnamon

    Present address: Institute of Animal Science, ARO, The Volcani Center, PO Box 6, Bet Dagan, 50250, Israel

Authors and Affiliations

  1. The Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel

    Esther Maor-Sagie, Yuval Cinnamon, Barak Yaacov, Avraham Shaag, Shamir Zenvirt, Carmelit Richler & Ayala Frumkin

  2. Department of Obstetrics and Gynecology, Hadassah Ein-Karem, Hebrew University Medical Center, Jerusalem, Israel

    Esther Maor-Sagie & Neri Laufer

  3. Department of Pathology, Hadassah, Hebrew University Medical Center, Jerusalem, Israel

    Hannoch Goldsmidt

Authors
  1. Esther Maor-Sagie
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  2. Yuval Cinnamon
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  3. Barak Yaacov
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  4. Avraham Shaag
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  5. Hannoch Goldsmidt
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  6. Shamir Zenvirt
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  7. Neri Laufer
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  8. Carmelit Richler
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  9. Ayala Frumkin
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Corresponding author

Correspondence to Esther Maor-Sagie.

Additional information

Capsule Splice site mutation in the SynaptonemaL Complex central Element 1 resulted in non obstructive azoopsermia in two siblings. The results confirmed by immunohystochemistry on testicular samples.

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Maor-Sagie, E., Cinnamon, Y., Yaacov, B. et al. Deleterious mutation in SYCE1 is associated with non-obstructive azoospermia. J Assist Reprod Genet 32, 887–891 (2015). https://doi.org/10.1007/s10815-015-0445-y

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  • DOI: https://doi.org/10.1007/s10815-015-0445-y

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