Fragiles-X Syndrom

Fragile X syndrome is an X-linked neurodevelopmental disorder affecting both males and females. Phenotypical characteristics include intellectual deficits, somatic symptoms and behavioural abnormalities caused by loss of the FMRP protein, which leads to destruction of synapses with metabotropic glutamate receptors. The FMR1 gene harbours a CGG repeat in the 5’-untranslated region. The vast majority of fragile-X syndrome patients have a largely expanded CGG repeat (220 or more triplets, designated “full mutation”) and an inactive gene. Full mutation alleles originate upon proliferation of oogonia in the fetal ovary of females who carry a mitotically unstable premutation (59–200 repeats). Premutation carriers have no symptoms of fragile X syndrome; they may, however, experience premature ovarian insufficiency and/or fragile X-associated tremor/ataxia syndrome. The diagnosis of both syndromes requires genetic testing to measure the number of CGG repeats. Prenatal diagnostics of fragile X syndrome is offered to females carrying a pre- or full mutation.