Association of GTF2i in the Williams-Beuren Syndrome Critical Region with Autism Spectrum Disorders
Duplications of 7q11.23, deleted in Williams-Beuren Syndrome, have been implicated in autism spectrum disorders (ASDs). A 1.5 Mb duplication was identified in one girl with severe expressive language deficits and anxiety among 1,142 ASD individuals screened for this duplication. Family-based association studies of Tag-SNPs in three genes (STX1A , CYLN2 and GTF2i) in two multiplex autism family cohorts revealed strong association of two GTF2i SNPs and their haplotype in Cohort 1 and the combined families. The risk alleles and haplotype were associated with severe problems in social interaction and excessive repetitive behaviors. Our findings suggest the GTF2i gene is important in the etiology of autism in individuals with this duplication and in non-duplication cases with severe social interaction problems and repetitive behaviors.
KeywordsAutism Spectrum Disorders (ASDs) Gene association GTF2i gene 7q11.23 duplication Williams-Beuren Syndrome (WBS)
This work was supported by an OMHF grant (PI: JJAH), a CIHR-IHRT grant (#43820) to JJAH (PI) and ASD-CARC (http://www.AutismResearch.com), CIHR grants (RT-64217: MESL, PI; MOP 74502: ERS, PI), Michael Smith Foundation for Health Research (MESL and ERS), on-going support from Ongwanada, and an OMHF studentship to PM. PM, YQ and NR are trainees with the CIHR/NAAR STIHR Inter-Institute ASDs Training Program (PI: JJAH) (http://www.AutismTraining.ca). This research was also supported, in part, by funds from the New York State Office of Mental Retardation and Developmental Disabilities. The authors are very grateful to the families who participated in this research through ASD-CARC (http://www.AutismResearch.com), and acknowledge the resources provided by the AGRE (Autism Genetics Resource Exchange) consortium and the participating AGRE families. AGRE is a program of Cure Autism Now and supported, in part, by grant MH64547 from the NIMH to Daniel H. Geschwind (PI). We thank Chris Hall for her excellent work managing our DNA Bank and preparing samples for these studies.
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