title: Capturing the fragile X premutation phenotypes: a collaborative effort across multiple cohorts.
abstract: OBJECTIVE
  To capture the neuropsychological profile among male carriers of the FMR1 premutation allele (55-200 CGG repeats) who do not meet diagnostic criteria for the late-onset fragile X-associated tremor/ataxia syndrome, FXTAS.
  
  
  METHODS
  We have initiated a multicenter collaboration that includes 3 independent cohorts, totaling 100 carriers of the premutation and 216 noncarriers. The initial focus of this collaboration has been on executive function. Four executive function scores are shared among the 3 cohorts (Controlled Oral Word Association Test, Stroop Color-Word Test, and Wechsler backward digit span and letter-number sequencing) whereas additional executive function scores are available for specific cohorts (Behavior Dyscontrol Scale, Hayling Sentence Completion Test Part B, and Wisconsin Card Sorting Test). Raw scores were analyzed by using statistical models that adjust for cohort-specific effects as well as age and education.
  
  
  RESULTS
  Carriers scored significantly lower compared to noncarriers on the Stroop Color-Word Test (p = .01), Hayling Sentence Completion Test Part B (p < .01), and Behavioral Dyscontrol Scale (p = .03), with the Hayling displaying a significant age-related decline (p = .01), as assessed by an age and repeat length-group interaction. Follow-up analysis of the collective data did not identify any specific age groups or repeat length ranges (i.e., low premutation = 55-70 repeats, midpremutation = 71-100 repeats, high premutation = 101-199 repeats) that were associated with an increased risk of executive function deficits.
  
  
  CONCLUSIONS
  Preliminary analyses do not indicate global executive function impairment among male carriers without FXTAS compared to noncarriers. However, impairment in inhibitory capacity may be present among a subset of carriers, though the risk factors for this group do not appear to be related to age or repeat length.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Jessica Ezzell
authors.initials: JE
authors.lastname: Hunter
authors.forename: Stephanie
authors.initials: S
authors.lastname: Sherman
authors.forename: Jim
authors.initials: J
authors.lastname: Grigsby
authors.forename: Cary
authors.initials: C
authors.lastname: Kogan
authors.forename: Kim
authors.initials: K
authors.lastname: Cornish
mesh_terms: D000483:Alleles; D001259:Ataxia / Q000235:genetics* / Q000503:physiopathology; D015331:Cohort Studies; D056344:Executive Function; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D010641:Phenotype; D013577:Syndrome; D014202:Tremor / Q000235:genetics* / Q000503:physiopathology; D019680:Trinucleotide Repeat Expansion
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human