Fragile-X syndrome and fragile X-associated tremor/ataxia syndrome: two faces of FMR1.
Recent advances in our understanding of the clinical and molecular features of the fragile-X mental-retardation 1 gene, FMR1, highlight the importance of single-gene disorders. 15 years after its discovery, FMR1 continues to reveal new and unexpected clinical presentations and molecular mechanisms. Loss of function of FMR1 is a model for neurodevelopmental and behavioural disorders, including mental retardation, autism, anxiety, and mood instability. In addition, overexpression and CNS toxicity of FMR1 mRNA causes a late-onset neurodegenerative disorder, the fragile-X-associated tremor/ataxia syndrome (FXTAS). A similar mechanism is probably involved in premature ovarian failure, which affects up to 20% of female carriers of an altered FMR1 gene.
Jacquemont
Sebastien
S
Service de Génétique, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. sebastien.jacquemont@chuv.ch
Hagerman
Randi J
RJ
Hagerman
Paul J
PJ
Leehey
Maureen A
MA
D000328:Adult; D001259:Ataxia / Q000188:drug therapy / Q000209:etiology*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000096:biosynthesis / Q000235:genetics*; D005600:Fragile X Syndrome / Q000150:complications* / Q000188:drug therapy / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008297:Male; D008593:Menopause / Q000235:genetics / Q000502:physiology; D008875:Middle Aged; D010375:Pedigree; D012333:RNA, Messenger; D012640:Seizures / Q000188:drug therapy / Q000209:etiology; D014202:Tremor / Q000188:drug therapy / Q000209:etiology*
D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; C497683:FMR1 protein, human