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

• Type of Material: Article
• Authors: Emily Allen, Emory University; Krista Charen, Emory University; Heather Hipp, Emory University; Lisa Shubeck, Emory University; Ashima Amin, Emory University; Weiya He, Emory University; Sarah L Nolin, New York State Inst Basic Res Dev Disabil; Anne Glicksman, New York State Inst Basic Res Dev Disabil; Nicole Tortora, New York State Inst Basic Res Dev Disabil; Bonnie McKinnon, Emory University; Katharine E Shelly, Emory University; Stephanie Sherman, Emory University
• Language: English
• Date: 2021-04-29
• Publisher: SPRINGERNATURE
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41436-021-01177-y
• Title of Journal or Parent Work: GENETICS IN MEDICINE
• Volume: 23
• Issue: 9
• Start Page: 1648
• End Page: 1655
• Grant/Funding Information: 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: WOMEN; PREMUTATION; AGE; INTERMEDIATE; INSTABILITY; Science & Technology; Genetics & Heredity; FAILURE; Life Sciences & Biomedicine; GENE; POPULATION; CARRIER; TREMOR/ATAXIA SYNDROME
• Research Categories: Health Sciences, Obstetrics and Gynecology

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.