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Abstract
FXTAS is a progressive neurodegenerative disorder characterized by problems with movement and cognition. FXTAS is a late-onset disorder, usually occurring after age 50, and its signs and symptoms gets worsen with age. In addition to neuropathy, thyroid dysfunctions, hypertension, immune dysfunction and cardiac arrhythmias are also observed in some FXTAS patient. The prevalence of FXTAS is estimated to range between 1 in 110 to 250 in females and 1 in 260 to 800 in males. However, due to incomplete penetrance it is estimated that 1 in ~3000 male and 1 in ~5000 female are at risk of developing FXTAS, with disease symptoms getting more pronounced with age. This condition affects males more frequently and severely than females. Affected individuals have areas of damage in the part of the brain including cerebellum, cerebral and cerebellar white matter, frontal cortex, and hippocampus which can be analyzed with magnetic resonance imaging (MRI).
At the histopathological level, FXTAS is characterized by neuronal cell loss and presence of large ubiquitin-positive intranuclear inclusions in both neurons and astrocytes. Rare ubiquitin positive inclusions are also observed in non-CNS organs like kidney and thyroid, At the genetic level, FXTAS is caused by the presence of 55 to 200 CGG repeats located within the 5’ untranslated region(UTR) of the Fragile X mental retardation1(FMR1) gene (OMIM *309550), located on the q-arm of the X chromosome. The FMR1 gene encodes FMRP which is RNA binding protein involved in regulation of transport and local translation of mRNAs in brain and is essential for synaptic plasticity and neuronal development. An expansion of CGG trinucleotide repeats within the 5’-UTR of FMR1 causes different neuropathological conditions based on the number of CGG repeats. FXTAS, Fragile Xassociated primary ovarian insufficiency (FXPOI) and Fragile X-associated Neuropsychiatric Disorders (FXAND) are caused by expansions of 55 to 200 CGG repeats (premutation, PM), while Fragile X syndrome (FXS) is caused by expansions greater than 200 CGG repeats (full mutation, FM). (Shortened by ProQuest.)