Tissue heterogeneity of the FMR1 mutation in a high-functioning male with fragile X syndrome

Few studies have been conducted comparing the FMR1 mutation in multiple tis sues of individuals affected with fragile X syndrome, We report a postmorte m study of the FMR1 mutation in multiple tissues from a high-functioning ma le with fragile X syndrome, This man was not mentally retarded and had only a few manifestations of the disorder such as learning disabilities and mil d attention problems, Southern blot analysis of leukocytes demonstrated an unmethylated mutation with a wide span of sizes extending from the premutat ion to full mutation range, A similar pattern was seen in most regions of t he brain, In contrast, a methylated full mutation of a single size was seen in the parietal lobe and in most non-brain tissues studied, Therefore, the re were striking differences in both FMR1 mutation size and methylation sta tus between tissues, Lack of mental retardation in this individual may have been due to sufficient expression of FMR1 protein (FMRP) in most areas of the brain, Immunocytochemistry showed FMRP expression in regions of the bra in with the unmethylated mutation (superior temporal cortex, frontal cortex , and hippocampus) and no expression in the region with the methylated full mutation (parietal), Neuroanatomical studies showed no dendritic spine pat hology in any regions of the brain analyzed. (C) 1999 Wiley-Liss, Inc.