Association and transmission analysis of the FMR1 IVS10 + 14C-T variant in autism.

Evidence from the high male to female ratio of individuals with autism as well as suggestive linkage data have implicated the possible involvement of X chromosomal loci in the aetiology of autism. Studies of the FMR1 gene on Xq27 have shown that occasionally individuals, and particularly females, with the [CGG] repeat expansion and methylation mutation may present with autistic symptoms. However, molecular studies suggest that such mutations are not a major cause of autism. Previously, we have screened autism probands for mutations in regions of the FMR1 gene downstream of the [CGG] repeat and identified an intronic variant in the FMR1 gene, IVS10 + 14C-T, which was present at a significantly higher frequency in autistic individuals compared to controls individuals. We have now investigated this variant in a further 136 autism families and 186 control individuals. We have established that the variant is significantly more frequent among East Asian individuals within our affected and control groups (P < 0.0001) and although we observed a trend of higher transmission frequency of the rare allele to affected individuals, there was no significant evidence in either family-based or case/control association studies for this variant in autism (P > 0.05). Copyright 2003 Wiley-Liss, Inc.