Towards An Understanding of Neuropsychiatric Manifestations In Fragile X Premutation Carriers

Abstract

Fragile X-associated disorders (FXD) are a group of disorders caused by expansion of non-coding CGG repeat elements in the fragile X (FMR1) gene. One of these disorders, fragile X syndrome (FXS), is the most common heritable cause of intellectual disability, and is caused by large CGG repeat expansions (>200) resulting in silencing of the FMR1 gene. An increasingly recognized number of neuropsychiatric FXD have recently been identified that are caused by ‘premutation’ range expansions (55-200). These disorders are characterized by a spectrum of neuropsychiatric manifestations ranging from an increased risk of neurodevelopmental, mood and anxiety disorders to neurodegenerative phenotypes such as the fragile X-associated tremor ataxia syndrome (FXTAS). Here, we review advances in the clinical understanding of neuropsychiatric disorders in premutation carriers across the lifespan and offer guidance for the detection of such disorders by practicing psychiatrists and neurologists.

Anxiety disorders in fragile X premutation carriers: Preliminary characterization of probands and non-probands

“…and recruitment methods to reduce bias, would help validate the findings of this preliminary report. Given our finding of significant anxiety, treatment of these problems needs to be considered by the clinician who cares for these individuals as we have recommended previously (57,58).…”

Study of the Genetic Etiology of Primary Ovarian Insufficiency: FMR1 Gene

“…At a cognitive level, 80%–90% of males with FXS present mild to moderate intellectual deficiency, with an important attention deficit and delayed development of speech and language. At a behavioral level, hyperactivity is characteristic, and one-third of individuals with FXS have autism [98,99]. Of these, 18%–36% meet the criteria for autism disorder (AD) and 43%–67% present an autistic spectrum disorder (ASD).…”

Impact of the MLL1 morphemes on codon utilization and preservation in CpG Islands

“…Well‐known examples include expansions observed within coding segments in homeotic genes ( i.e. HOXA13 and HOXD13 ), and in Fragile X (disorders caused by expansion of non‐coding CGG repeats in the FMR1 gene) . Occurrence of CGG/CCG repeats within coding exons produces amino acid runs (reiteration of an amino acid residue) in proteins …”