title: No evidence for a difference in neuropsychological profile among carriers and noncarriers of the FMR1 premutation in adults under the age of 50.
abstract: The 5' untranslated region of the fragile X mental retardation gene, FMR1, contains a polymorphic CGG repeat. Expansions of this repeat are associated with a spectrum of disorders. Full mutation alleles, repeats >or= 200, are associated with fragile X syndrome. Premutation alleles, repeats of approximately 55-199, are associated with a tremor-ataxia syndrome most commonly in older males and primary ovarian insufficiency in females. However, the neuropsychological impact of carrying a premutation allele is presently unclear in younger adults. In this study, we analyzed neuropsychological scores for 138 males and 506 females ascertained from the general population and from families with a history of fragile X syndrome. Subjects were age 18-50 years and had varying repeat lengths. Neuropsychological scores were obtained from measures of general intelligence, memory, and executive functioning, including attention. Principal component analysis followed by varimax rotation was used to create independent factors for analysis. These factors were modeled for males and females separately via a general linear model that accounted for correlation among related subjects. All models were adjusted for potential confounders, including age at testing, ethnicity, and household income. Among males, no repeat length associations were detected for any factor. Among females, only a significant association with repeat length and self-report attention (p < 0.01) was detected, with premutation carriers self-reporting significantly more attention-related problems compared to noncarriers. No significant interactions between repeat length and age were detected. Overall, these results indicate the lack of a global neuropsychological impact of carrying a premutation allele among adults under the age of 50.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Jessica Ezzell
authors.initials: JE
authors.lastname: Hunter
authors.forename: Emily Graves
authors.initials: EG
authors.lastname: Allen
authors.forename: Ann
authors.initials: A
authors.lastname: Abramowitz
authors.forename: Michele
authors.initials: M
authors.lastname: Rusin
authors.forename: Mary
authors.initials: M
authors.lastname: Leslie
authors.forename: Gloria
authors.initials: G
authors.lastname: Novak
authors.forename: Debra
authors.initials: D
authors.lastname: Hamilton
authors.forename: Lisa
authors.initials: L
authors.lastname: Shubeck
authors.forename: Krista
authors.initials: K
authors.lastname: Charen
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Sherman
mesh_terms: D000293:Adolescent; D000328:Adult; D001288:Attention; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D006580:Genetic Carrier Screening; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007360:Intelligence; D016014:Linear Models; D008297:Male; D008568:Memory; D008606:Mental Processes; D008875:Middle Aged; D009483:Neuropsychological Tests; D025341:Principal Component Analysis; D019680:Trinucleotide Repeat Expansion; D055815:Young Adult
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human