Health problems in females carriers of premutation in the FMR1 gene

Premutation in the FMR1 gene occur in the general population with an estimated prevalence 1 in 130-260 females and 1 in 250-810 males. Carriers of premutation are at risk of development of spectrum of neurological, psychiatric and immunological disorders in adulthood. Fragile X-associated disease caused by dynamic mutation (expansion of CGG repeats) can be divided into three disorders: FXS - Fragile X syndrome, FXPOI - Fragile X-associated primary ovarian insufficiency, FXTAS -Fragile X-associated tremor/ataxia syndrome, which can be present in few generations of one family. Immuno-mediated disorders are more common in premutation carriers as compared to control group, especially hypothyroidism and fibromyalgia. Although FMR1-associated conditions are not curable, timely diagnosis through genetic testing is important as it can lead to implementation of treatment strategies and behavioral interventions considered to improve symptoms. Knowledge of expanded allele status for females helps them to make more informed reproductive decisions.