carriersoftheFMR1premutation：FMR1前突变携带者的.pdfVIP

Grigsby et al. Journal of Neurodevelopmental Disorders 2014, 6:28 /content/6/1/28 REVIEW Open Access The cognitive neuropsychological phenotype of carriers of the FMR1 premutation 1,2* 3 4 3 5,6 5,7,8 Jim Grigsby , Kim Cornish , Darren Hocking , Claudine Kraan , John M Olichney , Susan M Rivera , 5,8 9 5,10 5,6 Andrea Schneider , Stephanie Sherman , Jun Yi Wang and Jin-Chen Yang Abstract The fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting a subset of carriers of the FMR1 (fragile X mental retardation 1) premutation. Penetrance and expression appear to be significantly higher in males than females. Although the most obvious aspect of the phenotype is the movement disorder that gives FXTAS its name, the disorder is also accompanied by progressive cognitive impairment. In this review, we address the cognitive neuropsychological and neurophysiological phenotype for males and females with FXTAS, and for male and female unaffected carriers. Despite differences in penetrance and expression, the cognitive features of the disorder appear similar for both genders, with impairment of executive functioning, working memory, and information processing the most prominent. Deficits in these functional systems may be largely responsible for impairment on other measures, including tests of general intelligence and declarative learning. FXTAS is to a large extent a white matter disease, and the cognitive phenotypes observed are consistent with what some have described as white matter dementia, in contrast