title: Clinical, molecular, and pharmacological aspects of FMR1 related disorders.
abstract: BACKGROUND
  Fragile X syndrome, the most common inherited cause of intellectual disability, is associated with a broad spectrum of disorders across different generations of a single family. This study reviews the clinical manifestations of fragile X-associated disorders as well as the spectrum of mutations of the fragile X mental retardation 1 gene (FMR1) and the neurobiology of the fragile X mental retardation protein (FMRP), and also provides an overview of the potential therapeutic targets and genetic counselling.
  
  
  METHODS
  This disorder is caused by expansion of the CGG repeat (>200 repeats) in the 5 prime untranslated region of FMR1, resulting in a deficit or absence of FMRP. FMRP is an RNA-binding protein that regulates the translation of several genes that are important in synaptic plasticity and dendritic maturation. It is believed that CGG repeat expansions in the premutation range (55 to 200 repeats) elicit an increase in mRNA levels of FMR1, which may cause neuronal toxicity. These changes manifest clinically as developmental problems such as autism and learning disabilities as well as neurodegenerative diseases including fragile X-associated tremor/ataxia syndrome (FXTAS).
  
  
  CONCLUSIONS
  Advances in identifying the molecular basis of fragile X syndrome may help us understand the causes of neuropsychiatric disorders, and they will probably contribute to development of new and specific treatments.
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Pugin
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile. Electronic address: vfaundes@inta.cl.
authors.forename: V
authors.initials: V
authors.lastname: Faundes
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile.
authors.forename: L
authors.initials: L
authors.lastname: Santa María
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile.
authors.forename: B
authors.initials: B
authors.lastname: Curotto
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile.
authors.forename: S
authors.initials: S
authors.lastname: Aliaga
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile.
authors.forename: I
authors.initials: I
authors.lastname: Salas
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile.
authors.forename: P
authors.initials: P
authors.lastname: Soto
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile.
authors.forename: P
authors.initials: P
authors.lastname: Bravo
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile.
authors.forename: M I
authors.initials: MI
authors.lastname: Peña
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile.
authors.forename: M A
authors.initials: MA
authors.lastname: Alliende
mesh_terms: D001259:Ataxia / Q000175:diagnosis / Q000235:genetics*; D001321:Autistic Disorder; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000494:pharmacology*; D005600:Fragile X Syndrome / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability; D009154:Mutation / Q000235:genetics; D012333:RNA, Messenger; D014202:Tremor / Q000175:diagnosis / Q000235:genetics*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; C497683:FMR1 protein, human
keywords: Autism spectrum disorders; Deoxyribonucleic acid methylation; Discapacidad intelectual; Fagile X mental retardation protein; Intellectual disability; Metilación del ADN; Proteína FMRP; Proteínas de unión al RNA; Ribonucleic acid-binding proteins; Trastornos del espectro autista