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Author Notes:

Emily Graves Allen, Email: emgrave@emory.edu

E.G.A., S.L.S., and H.S.H. were involved in the conceptualization of the project. Formal analyses and writing of the original draft was performed by E.G.A. Data curation was performed by K.C., L.S., and H.S.H. Laboratory analyses were performed by A.A., W.H., S.L.N., A.G., and N.T. Writing and methodology were completed by E.G.A., K.C., H.S.H., L.S., S.L.N., B.M., K.E.S., and S.L.S. Funding acquisition was done by E.G.A. and S.L.S.

First and foremost, we thank the families who participated in this project. Without their contribution and encouragement, this work could not be done. We would also like to thank the Fragile X Research Participant Registry of the Carolina Institute for Developmental Disabilities (P50 HD103573) at the University of North Carolina at Chapel Hill who helped with recruitment. Lastly, we want to thank the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Neurological Disorders and Stroke (NINDS) for supporting our National Fragile X Center (U54NS091859 and P50HD104463) in which this work was conducted.

The authors declare no competing interests.

Subject:

Research Funding:

This study was supported in part by the Emory Integrated Genomics Core (EIGC), which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities.

This study also utilized a REDCap database supported by Emory’s Library and Information Technology Services (UL1TR000424).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • TREMOR/ATAXIA SYNDROME
  • PREMUTATION
  • CARRIER
  • POPULATION
  • FAILURE
  • WOMEN
  • GENE
  • AGE
  • INTERMEDIATE
  • INSTABILITY

Refining the risk for fragile X-associated primary ovarian insufficiency (FXPOI) by FMR1 CGG repeat size

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Journal Title:

GENETICS IN MEDICINE

Volume:

Volume 23, Number 9

Publisher:

, Pages 1648-1655

Type of Work:

Article | Final Publisher PDF

Abstract:

Purpose: Approximately 20–30% of women with an FMR1 premutation experience fragile X–associated primary ovarian insufficiency (FXPOI); however, current risk estimates based on repeat size only identify women with the midrange of repeats to be at the highest risk. Methods: To better understand the risk by repeat size, we collected self-reported reproductive histories on 1,668 women and divided them into high-resolution repeat size bins of ~5 CGG repeats to determine a more accurate risk for FXPOI in relation to CGG repeat length. Results: As previously reported, women with 70–100 CGG repeats were at the highest risk for FXPOI using various statistical models to compare average age at menopause and risk of FXPOI, with women with 85–89 repeats being at the highest risk. Importantly, women with <65 repeats or >120 repeats did not have a significantly increased risk for FXPOI compared to women with <45 repeats. Conclusion: Using a large cross-section study on 1,668 women, we have provided more personalized risk assessment for FXPOI using high-resolution repeat size bins. Understanding the variability in risk has important implications for family planning and overall health among women with a premutation.

Copyright information:

© The Author(s) 2021

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
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