title: The emerging fragile X premutation phenotype: evidence from the domain of social cognition.
abstract: Fragile X syndrome is a neurodevelopmental disorder that is caused by large methylated expansions of a CGG repeat (>200) region upstream of the FMR1 gene that results in the lack of expression of the fragile X mental retardation protein (FMRP). Affected individuals display a neurobehavioral phenotype that includes a significant impairment in social cognition alongside deficits in attentional control, inhibition and working memory. In contrast, relatively little is known about the trajectory and specificity of any cognitive impairment associated with the fragile X premutation ("carrier-status") (approximately 55-200 repeats). Here, we focus on one aspect of cognition that has been well documented in the fragile X full mutation, namely social cognition. The results suggest that premutation males display a pattern of deficit similar in profile, albeit milder in presentation, to that of the full mutation. However, little evidence emerged for a correlation between CGG repeat length and severity of phenotypic outcomes. The findings are discussed in the context of functional neuroimaging and brain-behaviour-molecular correlates. We speculate that the deficiencies in social cognition are attributable to impairment of neural pathways modulated by the cerebellum.
authors.affiliation: Neuroscience Laboratory for Research and Education in Neurodevelopmental Disorders, McGill University, Montreal, Canada. kim.cornish@mcgill.ca
authors.forename: Kim
authors.initials: K
authors.lastname: Cornish
authors.forename: Cary
authors.initials: C
authors.lastname: Kogan
authors.forename: Jeremy
authors.initials: J
authors.lastname: Turk
authors.forename: Tom
authors.initials: T
authors.lastname: Manly
authors.forename: Nicole
authors.initials: N
authors.lastname: James
authors.forename: Andrea
authors.initials: A
authors.lastname: Mills
authors.forename: Ann
authors.initials: A
authors.lastname: Dalton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004644:Emotions / Q000502:physiology; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000150:complications / Q000235:genetics* / Q000523:psychology*; D006579:Heterozygote; D006801:Humans; D007092:Imagination / Q000502:physiology; D007360:Intelligence; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics*; D021641:Recognition, Psychology / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012720:Severity of Illness Index; D012938:Social Perception
chemical_list: D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human