# Aging Symptom Trajectories in Mother Carriers of the FMR1 Premutation

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2024 · $10,826

## Abstract

PROJECT SUMMARY/ABSTRACT
 About 1 in 151 women in the US are carriers of a genetic abnormality called the FMR1 premutation
(FXpm). Mothers who carry the FXpm are at risk for passing the mutated gene to their children, which may result
in fragile X syndrome. The FXpm is also associated with substantially increased risk for disease, including
neurodegenerative disease, premature menopause, psychiatric involvement, and executive and social deficits.
New evidence suggests that FXpm carrier mothers may experience premature age-related decline across
multiple symptom domains. The aging expression of FXpm phenotype is particularly concerning when applied
within the context of fragile X families because these symptoms impact not only the carrier mother, but also her
ability to care and advocate for her children with fragile X syndrome. However, almost all evidence of age-
related decline in this group has been gleaned from cross-sectional data that are insufficient for drawing robust
longitudinal trajectories. This represents a substantial barrier to effective clinical management, as we lack the
data needed to understand the long-term effects of the FXpm genotype and its implications for families.
 This proposal seeks to determine the stability of key FXpm phenotypes (mental health, executive, social)
across midlife and early old age in FXpm carrier mothers compared to healthy controls (Aim 1); investigate
autonomic and molecular-genetic factors associated with age-related symptom expression and their interface
with parenting stress (Aim 2); and evaluate functional limitations associated with FXpm symptoms across age
(Aim 3). We will accomplish these aims by adopting an accelerated longitudinal design to track age-related
change occurring across 45-80 years in 75 FXpm carrier mothers compared to 75 control mothers. The over-
arching goal is to inform the critical age periods and risk factors in age-related decline, as well as to lay the
groundwork for future mechanistic studies. This work is necessary to develop strategies to ameliorate FXpm
symptoms, which will improve outcomes for both FXpm carrier mothers and their children with fragile X
syndrome.

## Key facts

- **NIH application ID:** 11089002
- **Project number:** 3R01AG073374-03S1
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Jessica Klusek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $10,826
- **Award type:** 3
- **Project period:** 2022-07-15 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11089002

## Citation

> US National Institutes of Health, RePORTER application 11089002, Aging Symptom Trajectories in Mother Carriers of the FMR1 Premutation (3R01AG073374-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11089002. Licensed CC0.

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