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. Reelin, a protein involved in neuronal migration during development, is encoded by a gene located on 7q22, within the candidate region on 7q showing increased allele sharing in previous genome scans. 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. 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.
INSERM E0117, University of Paris V, Department of Mental Health and Therapeutics, Sainte-Anne Hospital, 75014 Paris, France. krebs@chsa. broca.inserm.fr
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Krebs
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Betancur
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Leroy
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Bourdel
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Gillberg
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Leboyer
D020121:5' Untranslated Regions / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D018911:Trinucleotide Repeats
D020121:5' Untranslated Regions; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases