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Defining the role of FMR1 gene in unexplained recurrent spontaneous abortion

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

Abstract

Introduction

Recurrent spontaneous abortion is a multifactorial disorder and till date, various factors have been attributed in its pathogenesis. Still, approximately 50% of RSA cases remain unexplained. Premutation (PM) expanded allele of fragile-X mental retardation 1 (FMR1) gene is known to contribute to ovarian dysfunction in 20% of the cases. Recently, the link between expanded FMR1 allele and recurrent miscarriages has been reported.

Method

In the present prospective case–control study, we have investigated the status of CGG repeat size at 5′UTR of the FMR1 gene in women with unexplained RSA in comparison to age-matched healthy control women (n = 100 each). The genomic DNA from these samples was subjected to molecular analysis for characterization of CGG repeat size and composition at FMR1 gene

Results

As compared to the control women, the RSA women cohort had a higher frequency of carriers with alleles in gray zone (GZ) and expanded PM range, i.e., 2% (2/100) versus 5% (5/100), respectively. Also, the RSA cohort had a significantly higher number of normal alleles with ≥ 35 CGG repeats (24 out of 200 alleles) as compared to control cohort (8 out of 200 alleles). The number of larger FMR1 alleles with pure CGG repeat tract was found to be significantly higher (P = 0.0063) in the RSA cohort (15 out of 200 alleles) as compared to that in control cohort (3 out of 200 alleles).

Conclusion

Henceforth, the CGG expanded uninterrupted FMR1 allele might be associated with recurrent abortions and may help to explain many of these unexplained cases.

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Acknowledgements

The authors are grateful to the SGPGI of Medical Sciences, Lucknow, Uttar Pradesh, India, for providing the infrastructure for the research work. DDD is thankful Council of Science and Industrial Research (CSIR)–New Delhi for providing her fellowship.

Funding

This study was supported by the intramural project grant funded by the SGPGI of Medical Sciences, Lucknow, India (2015-36-IMP-83).

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Authors and Affiliations

  1. Dept of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, U.P., India

    Deepika Delsa Dean, Sarita Agarwal & Srinivasan Muthuswamy

  2. Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226014, India

    Sarita Agarwal

  3. Department of Life Science, National Institute of Technology Rourkela, Odisha, 769008, India

    Srinivasan Muthuswamy

Authors
  1. Deepika Delsa Dean
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Correspondence to Sarita Agarwal.

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The study was approved by the institutional ethical committee (IEC: 2016-28-PHD-90) and informed consent was obtained from the cases and controls.

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The authors declare that they have no conflict of interest.

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Dean, D.D., Agarwal, S. & Muthuswamy, S. Defining the role of FMR1 gene in unexplained recurrent spontaneous abortion. J Assist Reprod Genet 36, 2245–2250 (2019). https://doi.org/10.1007/s10815-019-01591-x

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