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A report of two homozygous TERB1 protein-truncating variants in two unrelated women with primary infertility

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

Abstract

Purpose

To investigate the genetic etiology of patients with female infertility.

Methods

Whole Exome Sequencing was performed on genomic DNA extracted from the patient’s blood. Exome data were filtered for damaging rare biallelic variants in genes with possible roles in reproduction. Sanger sequencing was used to validate the selected variants and segregate them in family members.

Results

A novel homozygous likely pathogenic variant, c.626G>A, p.Trp209*, was identified in the TERB1 gene of the patient. Additionally, we report a second homozygous pathogenic TERB1 variant, c.1703C>G, p.Ser568*, in an infertile woman whose azoospermic brother was previously described to be homozygous for her variant.

Conclusions

Here, we report for the first time two homozygous likely pathogenic and pathogenic TERB1 variants, c.626G>A, p.Trp209* and c.1703C>G, p.Ser568*, respectively, in two unrelated women with primary infertility. TERB1 is known to play an essential role in homologous chromosome movement, synapsis, and recombination during the meiotic prophase I and has an established role in male infertility in humans. Our data add TERB1 to the shortlist of Meiosis I genes associated with human infertility in both sexes.

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Acknowledgements

We thank the patients and their relatives for participating in this study, Christina Burhöi for her technical support, Dr. Sophie A. Koser for contacting the study participants, and Mohamed Ramadan for providing his consultation. We acknowledge the use of the Centre d’expertise et de services Génome Québec. This work was supported by the Canadian Institute of Health Research (PJT—180509, OGB – 177939, and PJT—155998). ZY was supported by Mitacs Accelerate (Ref. IT31962). ML was supported by the Research Institute of the McGill University Health Centre Desjardins Studentship, McGill University Faculty of Medicine Internal Studentship, and Travel Funding Support from Réseau Québécois en Reproduction and the Department of Human Genetics of McGill University. CF and FT were supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) sponsored Clinical Research Unit ‘Male Germ Cells’ (CRU326, project number 329621271).

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Authors and Affiliations

  1. Department of Human Genetics, McGill University Health Centre, Montreal, QC, Canada

    Zeynep Yalcin, Manqi Liang, Eric Bareke, Jacek Majewski & Rima Slim

  2. Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt

    Ibrahim M. Abdelrazek, Amira Nabil & Ebtesam Abdalla

  3. Institute of Reproductive Genetics, University of Münster, 48149, Münster, Germany

    Corinna Friedrich & Frank Tüttelmann

  4. OriginElle Fertility Clinic, Montreal, QC, Canada

    Seang-Lin Tan

  5. Department of Obstetrics and Gynecology, McGill University, Montreal, QC, Canada

    Seang-Lin Tan & Rima Slim

  6. Research Institute of the McGill University Health Centre, 1001 Décarie Blvd, Montréal, Québec, H4A 3J1, Canada

    Rima Slim

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  1. Zeynep Yalcin
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Correspondence to Rima Slim.

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Yalcin, Z., Liang, M., Abdelrazek, I. et al. A report of two homozygous TERB1 protein-truncating variants in two unrelated women with primary infertility. J Assist Reprod Genet 41, 751–756 (2024). https://doi.org/10.1007/s10815-024-03031-x

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