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Updated: May 30, 2026

Dissecting Cell-Autonomous Function of Fragile X Mental Retardation Protein in an Auditory Circuit by In Ovo Electroporation
Published on: July 6, 2022
Aberrant frontal lobe maturation in adolescents with fragile X syndrome is related to delayed cognitive maturation
Signe Bray1, Melissa Hirt, Booil Jo
1Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Background:
Fragile X syndrome (FXS) is the most common known heritable cause of intellectual disability. Prior studies in FXS have observed a plateau in cognitive and adaptive behavioral development in early adolescence, suggesting that brain development in FXS may diverge from typical development during this period.
Methods:
In this study, we examined adolescent brain development using structural magnetic resonance imaging data acquired from 59 individuals with FXS and 83 typically developing control subjects aged 9 to 22, a subset of whom were followed up longitudinally (1-5 years; typically developing: 17, FXS: 19). Regional volumes were modeled to obtain estimates of age-related change.
Results:
We found that while structures such as the caudate showed consistent volume differences from control subjects across adolescence, prefrontal cortex (PFC) gyri showed significantly aberrant maturation. Furthermore, we found that PFC-related measures of cognitive functioning followed a similarly aberrant developmental trajectory in FXS.
Conclusions:
Our findings suggest that aberrant maturation of the PFC during adolescence may contribute to persistent or increasing intellectual deficits in FXS.
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