Lessons from fragile X regarding neurobiology, autism, and neurodegeneration

J Dev Behav Pediatr. 2006 Feb;27(1):63-74. doi: 10.1097/00004703-200602000-00012.

Abstract

The fragile X mental retardation 1 gene (FMR1) mutation causes two disorders: fragile X syndrome (FXS) in those with the full mutation and the fragile X-associated tremor/ataxia syndrome (FXTAS) in some older individuals with the premutation. FXS is caused by a deficiency of the FMR1 protein (FMRP) leading to dysregulation of many genes that create a phenotype with ADHD, anxiety, and autism. FXTAS is caused by the elevation of FMR1-mRNA to levels 2 to 8 times normal in the premutation. This causes an RNA gain of function toxicity leading to brain atrophy, white matter disease, neuronal and astrocytic inclusion formation, and subsequent ataxia, intention tremor, peripheral neuropathy, and cognitive decline. The neurobiology and pathophysiology of FXS and FXTAS are described in detail.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Alleles
  • Animals
  • Anxiety Disorders / diagnosis
  • Anxiety Disorders / genetics
  • Anxiety Disorders / psychology
  • Attention Deficit Disorder with Hyperactivity / diagnosis
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Autistic Disorder / diagnosis
  • Autistic Disorder / genetics*
  • Autistic Disorder / psychology
  • Child
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Female
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Syndrome / diagnosis
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / psychology
  • Genetic Carrier Screening
  • Genetic Counseling
  • Genetic Testing
  • Heredodegenerative Disorders, Nervous System / diagnosis
  • Heredodegenerative Disorders, Nervous System / genetics*
  • Heredodegenerative Disorders, Nervous System / psychology
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Intellectual Disability / psychology
  • Male
  • Pedigree
  • Phenotype
  • RNA, Messenger / genetics
  • Trinucleotide Repeats

Substances

  • FMR1 protein, human
  • RNA, Messenger
  • Fragile X Mental Retardation Protein