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Arnold School of Public Health

Study sheds light on age-related vulnerabilities faced by women who carry FMR1 premutation

February 23, 2022 | Erin Bluvas,

Communication sciences and disorders associate professor Jessica Klusek and researchers from the South Carolina Family Experiences Lab have completed a study that offers new insights into the array of age-related symptoms and disorders that may affect women who carry the premutation allele of the FMR1 gene. An expert in FMR1-associated disorders, such as fragile X syndrome (the most common single-gene cause of autism spectrum disorder), Klusek’s work often adopts a family approach.

Her research program focuses on two overlapping aims: 1) communication features associated with autism and fragile X syndrome, which she supports as a co-investigator on a $3.1 million grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development, and 2) the effects of the FMR1 premutation on the 1 in 151 women who carry it (funded by an Early Career Award from National Institute on Deafness and Other Communication Disorders). 

“Women who carry the FMR1 premutation are at increased vulnerability to a decline in cognitive skills and physical health,” says Klusek, who notes that about 15 percent of carriers develop an age-related neurodegenerative disease called fragile X associated tremor/ataxia syndrome (FXTAS). “This particular genetic mutation has been understudied, so we have a poor understanding of who is most at risk for neurodegenerative disease, including the potential role of family history and genetic factors.”  

Previous research has linked the early decline in communication abilities (e.g., syntactic/grammatical complexity) with other forms of premature or atypical aging (e.g., Alzheimer’s disease). With this longitudinal study, published in the Journal of Neurodevelopmental Disorders, the researchers investigated whether women with the FMR1 premutation exhibited early communication decline which might indicate risk for neurodegenerative disease. They also looked at associations with certain features of the premutation (i.e., the gene’s CGG repeat length) and family history of FXTAS. 

Over a five-year period, the researchers collected language samples, family history information and CGG repeat length information (via molecular genetic testing) from 45 women (ages 35-64), who have the FMR1 premutation and at least one child with confirmed fragile X syndrome. Their analyses revealed that women in their mid-50s who reported a family history of FXTAS exhibited faster age-related decline in syntactic complexity than their counterparts without a family history. CGG repeat length was not a significant predictor of age-related change.

“Our findings of age-related decline in communication ability among individuals who have a family history of FXTAS suggests that these individuals may be at heightened risk for neurodegenerative disease,” Klusek says.  “These findings suggest that family history may need to be considered as a personalized risk factor for mothers with the FMR1 premutation. Early and targeted prevention, detection and treatment efforts to preserving health for this population are especially important because these mothers often continue to provide daily care and assistance for their children with fragile X syndrome throughout midlife.” 

This research was supported by the National Institutes of Health: R03HD098291, R21DC017804, F32DC013934 (PI: Klusek); R01HD024356 and P50HD103526 (PI: Abbeduto); and the Research Participant Registry Core of the Carolina Institute for Developmental Disabilities (P50HD103573).


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