Zespół łamliwego Chromosomu x i Choroby FMR1-zależne - Objawy Kliniczne, Epidemiologia i Podłoże Molekularne Choroby

Fragile X syndrome (FXS) is the second most common inherited cause of intellectual disability (ID), after Down syndrome. The severity of ID in FXS patients varies and depends mainly on the patient’s sex. Besides intellectual disorders, additional symptoms, such as psychomotor delay, a specific behavioral phenotype, or emotional problems are present in FXS patients. In over 99% of the cases, the disease is caused by the presence of a dynamic mutation in the FMR1 gene localized on the X chromosome. Due to the expansion of CGG nucleotides (over 200 repeats), FMR1 gene expression is decreased and results in the significant reduction of the FMRP protein level. The CGG expansion to premutation range (55-200 CGG repeats) is equivalent to the FXS carrier status and may cause FMR1-dependent disorders − fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS). In contrast to FXS, clinical symptoms of these diseases occur later in adulthood. The aim of the article is to present the knowledge about the molecular background and epidemiology of fragile X syndrome and other FMR1-related disorders.