INVITED SPEAKERS / COMUNICAÇÕES POR CONVITE

 

CC-09

FMR1 associated pathologies

 

 

Montserrat Milà^I

^IBioquímica i Genètica Molecular, Hospital Clinic, Barcelona, Spain. E-mail: MMILA@clinic.ub.es

 

 

Fragile X syndrome is the most common form of inherited mental retardation with a prevalence of approximately 1:2,466 men and 1:8,333 women in the Caucasian population. The molecular basis of the syndrome is predominantly a CGG expansion in the 5´untranslated region of the FMR1 gene. In the general population, individuals carry 6 to 55 repeats, and the triplet number is usually stably transmitted. Individuals with alleles between 55 and 200 CGG repeats are called premutated carriers and those with more than 200 CGG are considered to carry full mutations and present classical Fragile X syndrome. In the premutated range, the CGG number is unstable through transmission to the next generation and tends to expand. Diagnosis is based on the determination of the CGG number. FMR1 premutationismuchmorefrequentthanpreviouslythought. The most relevant pathologies associated with premutation have been described to be Fragile X premature ovarian insufficiency (FXPOI) and Fragile X tremor ataxia syndrome (FXTAS). Other clinical manifestations, associated with this premutation, were later identified as thyroid dysfunction, chronic muscle pain or fibromyalgia, among others. While FXPOI and FXTAS are definitively related, the latter manifestations require further studies. Here we revise the current knowledge of the individuals carrying FMR1 premutation.