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

Abstract

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][4][5][6][7][8] A case/control and familybased association study recently reported a positive association between a trinucleotide repeat polymorphism (GGC) located in the 5Ј untranslated region (UTR) of the reelin gene and autism. 9 We performed a transmission disequilibrium test (TDT) analysis of the 5ЈUTR 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.

Alleles of a reelin CGG repeat do not convey liability to autism in a sample from the CPEA network

“…Our findings agree with those recently published by Krebs et al [2002], who analyzed a sample of 117 simplex and 50 multiplex families. The estimated allele distribution from our families is quite similar to that estimated by both the Persico and Krebs studies, showing two common alleles with 8 and 10 CGG repeats, a few uncommon alleles (12 and 13 CGG repeats) and a smattering of rare alleles (4, 9, 11, 14, and 15 repeats).…”

“…If that were the case, RELN might play a small role in autism liability but its effects could be absent from our sample. Nonetheless, ours results and that of Krebs et al [2002] suggest that the CGG alleles in the 5 0 region of RELN cannot play a major role in autism liability. While our analysis does not support RELN as a susceptibility locus for autism, this gene may still be important in autism etiology.…”

A heterogeneity-based genome search meta-analysis for autism-spectrum disorders

“…region before the start codon, have reached conflicting results. [43][44][45][46][47][48][49] This may reflect only the common pattern of nonreplication of early claims from small studies 50 or a modest effect may still be present. A large study should be conducted on this association.…”

The genetics of autistic disorders and its clinical relevance: a review of the literature

“…Three studies did find an association, [176][177][178] five other studies of comparable size and power did not find an association of the 5 0 UTR trinucleotide or other variants with AD. [179][180][181][182][183] The first positive finding 176 reported an association with the relatively rare longer alleles ( > 10) of the 5 0 UTR trinucleotide polymorphism with AD. However, in another study, 178 the most common repeat 10 was over-represented in AD.…”