Absence of association between a polymorphic GGC repeat in the 5 ' untranslated region of the reelin gene and autism

Autism is a complex neurodevelopmental disorder with severe cognitive and communication disabilities, that has a strong genetic predisposition.(1) Reelin, a protein involved in neuronal migration during development, is encoded by a gene located on 7q22,(2) within the candidate region on 7q showing increased allele sharing in previous genome scanS.(3-8) A case/control and family-based association study recently reported a positive association between a trinucleotide repeat polymorphism (GGC) located in the 5' untranslated region (UTR) of the reelin gene and autism.(9) We performed a transmission disequilibrium test (TDT) analysis of the 5, UTR polymorphism in 167 families including 218 affected subjects (117 trios and 50 affected sib pairs) and found no evidence of linkage/association. Our results do not support previous findings and suggest that this GGC polymorphism of the reelin gene is unlikely to be a major susceptibility factor in autism and/or genetic heterogeneity.