Neurobehavioral phenotype in carriers of the fragile X premutation

There have been contradictory findings in the fragile X (fraX) literature a bout possible neurocognitive and psychological symptoms due to the fraX pre mutation (pM). The purpose of the present study was to investigate the rela tionship between CGG repeat length and neurobehavioral functioning in carri ers of the fraX pM. Eighty-five female carriers of the pM with allele sizes ranging from 59-166 were administered a comprehensive IQ test (WAIS-III) a nd completed a questionnaire designed to measure psychopathology (Symptom C hecklist (SCL)-90-R). No relationship between allele size and cognition was identified. A significant negative relationship between allele size and ag e was found, as well as a positive relationship between allele size and dep ression. Followup analyses separating small and large allele sizes (below a nd above 100 CGG repeats) indicated that individuals with larger allele siz es scored significantly higher on the Interpersonal Sensitivity and Depress ion subscales of the SCL-90-R. Despite the limitation of few individuals wi th high CGG repeat lengths, our findings suggest that females with larger p remutated alleles (greater than or equal to 100 repeats) display some clini cal manifestations of fraX syndrome. (C) 2001 Wiley-Liss, Inc.