title: Association and transmission analysis of the FMR1 IVS10 + 14C-T variant in autism.
abstract: 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).
authors.affiliation: Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. john_vincent@camh.net
authors.forename: John B
authors.initials: JB
authors.lastname: Vincent
authors.forename: Sandy
authors.initials: S
authors.lastname: Thevarkunnel
authors.forename: Debbie
authors.initials: D
authors.lastname: Kolozsvari
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Paterson
authors.forename: Wendy
authors.initials: W
authors.lastname: Roberts
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D016601:RNA-Binding Proteins; D018911:Trinucleotide Repeats / Q000235:genetics*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human