WHAT IS ALREADY KNOWN ON THIS TOPIC
This study supports a multidimensional model of FMR1 premutation biology in which CGG repeat structure, maternal age and FMR1 mRNA levels contribute to the risk of multigenerational expansion.
In addition, the evidence shows that somatic instability associated with neuropsychiatric outcomes, including depression, attention-deficit/hyperactivity disorders and anxiety symptom severity.
These findings suggest that somatic instability may serve as a useful biomarker for neuropsychiatric outcomes in female carriers with FMR1 premutation; therefore, future studies should prioritise tissue-specific instability profiling, longitudinal monitoring of CGG repeat dynamics and prospective evaluation of psychiatric outcomes.
The CGG trinucleotide repeat in the 5’ untranslated region of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is associated with numerous repeat expansion diseases and comorbidities when expanded beyond the threshold of 55 repeats. Repeats between 55 and 200 CGGs are…