Capturing the fragile X premutation phenotypes: a collaborative effort across multiple cohorts

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. Method: 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