The fragile X family of disorders

A model for autism and targeted treatments

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

CGG-repeat expansion mutations of the fragile X mental retardation 1 (FMR1) gene are the leading known cause of autism and autism spectrum disorders (ASD). Full mutation expansions (>200 CGG repeats) of the gene are generally silenced, resulting in absence of the FMR1 protein and fragile X syndrome. By contrast, smaller expansions in the premutation range (55-200 CGG repeats) result in excess gene activity and RNA toxicity, which is responsible for the neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), and likely additional cases of developmental delay and autism. Thus, the FAM1 gene is causative of a common (autism) phenotype via two entirely different pathogenic mechanisms, RNA toxicity and gene silencing. The study of this gene and its pathogenic mechanisms therefore represents a paradigm for understanding gene-brain relationships and the means by which diverse genetic mechanisms can give rise to a common behavioral phenotype.

Original languageEnglish (US)
Pages (from-to)40-52
Number of pages13
JournalCurrent Pediatric Reviews
Volume4
Issue number1
DOIs
StatePublished - Feb 2008

Fingerprint

Autistic Disorder
Genes
Fragile X Mental Retardation Protein
Phenotype
Fragile X Syndrome
Mutation
Gene Silencing
RNA Interference
Intellectual Disability
Neurodegenerative Diseases
RNA
Brain

Keywords

  • CGG repeat
  • Fragile X mental retardation 1 gene
  • Idiopathic Autism
  • Methyl-CpG binding protein
  • Neuroimaging

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

The fragile X family of disorders : A model for autism and targeted treatments. / Hagerman, Randi J; Rivera, Susan M.; Hagerman, Paul J.

In: Current Pediatric Reviews, Vol. 4, No. 1, 02.2008, p. 40-52.

Research output: Contribution to journalArticle

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