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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Cognitive and behavioral performance among FMR1 high-repeat allele carriers surveyed from special education classes.

The fragile X syndrome is caused by an unstable CGG repeat sequence in the 5' untranslated region of the X-linked, FMR1 gene. When the number of repeats exceeds 200, the region is hypermethylated and the gene is silenced. The lack of the protein produced by the FMR1 gene, FMRP, causes the fragile X syndrome. Recent evidence suggests that FMR1 alleles with unmethylated long repeat tracks (40-200 repeats) may cause a specific somatic phenotype in women, premature ovarian failure, and may cause variation in the levels of FMR1 mRNA and FMRP. Because FMR1 is known to be involved in the regulation of subset of genes expressed in the brain, we investigated the variation in cognitive and/or behavioral performance among carriers of high repeat alleles. Specifically, we administered cognitive, behavioral, and adaptive performance tests to children identified with high repeat alleles who attended special education classes in Atlanta, Georgia public schools and to those with < 40 repeats drawn from the same population. Overall, we found no significant effect of repeat size and the psychometric measures in our test battery after adjustment for multiple comparisons. All scales were found to be within 1 SD standard deviation of the mean. We did find an intriguing, albeit marginally statistically significant, association in the cognitive profile among males and not females, consistent with an X-linked effect. After adjusting for the overall cognitive abilities score, Verbal Ability scores decreased and Nonverbal Reasoning scores increased with repeat number to a greater extent in males than females. Spatial Ability scores were not associated with repeat number.[1]


  1. Cognitive and behavioral performance among FMR1 high-repeat allele carriers surveyed from special education classes. Sherman, S.L., Marsteller, F., Abramowitz, A.J., Scott, E., Leslie, M., Bregman, J. Am. J. Med. Genet. (2002) [Pubmed]
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