title: Neurodevelopmental effects of the FMR-1 full mutation in humans.
abstract: Brain dysfunction is the most important sequelae of the fragile X (FMR-1) mutation, the most common heritable cause of developmental disability. Using magnetic resonance imaging (MRI) and quantitative morphometry, we have compared the neuroanatomy of 51 individuals with an FMR-1 mutation with matched controls and showed that subjects with an FMR-1 mutation have increased volume of the caudate nucleus and, in males, the lateral ventricle. Both caudate and lateral ventricular volumes are correlated with IQ. Caudate volume is also correlated with the methylation status of the FMR-1 gene. Neuroanatomical differences between two monozygotic twins with an FMR-1 mutation who are discordant for mental retardation are localized to the cerebellum, lateral ventricles and subcortical nuclei. These findings suggest that the FMR-1 mutation causing the fragile X syndrome leads to observable changes in neuroanatomy that may be relevant to the neurodevelopmental disability and behavioural problems observed in affected individuals.
authors.affiliation: Kennedy Krieger Institute, Baltimore, Maryland 21205, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Reiss
authors.forename: M T
authors.initials: MT
authors.lastname: Abrams
authors.forename: R
authors.initials: R
authors.lastname: Greenlaw
authors.forename: L
authors.initials: L
authors.lastname: Freund
authors.forename: M B
authors.initials: MB
authors.lastname: Denckla
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001921:Brain / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000378:metabolism; D004200:Diseases in Twins / Q000235:genetics* / Q000523:psychology; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000473:pathology* / Q000523:psychology; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007360:Intelligence; D008279:Magnetic Resonance Imaging; D008297:Male; D016555:Matched-Pair Analysis; D008745:Methylation; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D012737:Sex Factors; D014430:Twins, Monozygotic
chemical_list: D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human