Journal of Autism and Developmental Disorders

, Volume 42, Issue 7, pp 1459–1469 | Cite as

Association of GTF2i in the Williams-Beuren Syndrome Critical Region with Autism Spectrum Disorders

  • Patrick Malenfant
  • Xudong Liu
  • Melissa L. Hudson
  • Ying Qiao
  • Monica Hrynchak
  • Noémie Riendeau
  • M. Jeannette Hildebrand
  • Ira L. Cohen
  • Albert E. Chudley
  • Cynthia Forster-Gibson
  • Elizabeth C. R. Mickelson
  • Evica Rajcan-Separovic
  • M. E. Suzanne Lewis
  • Jeanette J. A. Holden
Original Paper

Abstract

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.

Keywords

Autism Spectrum Disorders (ASDs) Gene association GTF2i gene 7q11.23 duplication Williams-Beuren Syndrome (WBS) 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Patrick Malenfant
    • 1
    • 2
    • 3
  • Xudong Liu
    • 2
    • 3
    • 4
  • Melissa L. Hudson
    • 2
    • 3
    • 4
  • Ying Qiao
    • 3
    • 5
    • 6
  • Monica Hrynchak
    • 7
  • Noémie Riendeau
    • 3
    • 6
  • M. Jeannette Hildebrand
    • 3
    • 6
  • Ira L. Cohen
    • 3
    • 8
    • 9
  • Albert E. Chudley
    • 3
    • 10
  • Cynthia Forster-Gibson
    • 3
    • 11
  • Elizabeth C. R. Mickelson
    • 3
    • 12
  • Evica Rajcan-Separovic
    • 3
    • 5
  • M. E. Suzanne Lewis
    • 3
    • 6
  • Jeanette J. A. Holden
    • 1
    • 2
    • 3
    • 4
    • 13
  1. 1.Department of PhysiologyQueen’s UniversityKingstonCanada
  2. 2.Autism Research Program & Genomics and Genetics Research LaboratoryOngwanada Resource CentreKingstonCanada
  3. 3.Autism Spectrum Disorders–Canadian-American Research ConsortiumKingstonCanada
  4. 4.Department of PsychiatryQueen’s UniversityKingstonCanada
  5. 5.Department of PathologyUniversity of British ColumbiaVancouverCanada
  6. 6.Department of Medical GeneticsUniversity of British Columbia and BC Child and Family Research InstituteVancouverCanada
  7. 7.Department of Laboratory Medicine, Cytogenetic LaboratoryRoyal Columbian HospitalNew WestminsterCanada
  8. 8.Department of PsychologyNew York State Institute for Basic Research in Developmental DisabilitiesStaten IslandUSA
  9. 9.George A. Jervis ClinicNew York State Institute for Basic Research in Developmental DisabilitiesStaten IslandUSA
  10. 10.WRHA Program in Genetics & Metabolism, Departments of Pediatrics and Child Health, Biochemistry and Medical GeneticsUniversity of ManitobaWinnipegCanada
  11. 11.Department of Family MedicineQueen’s UniversityKingstonCanada
  12. 12.Department of PediatricsUniversity of British ColumbiaVancouverCanada
  13. 13.Centre for Neuroscience StudiesQueen’s UniversityKingstonCanada

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