title: An atypical deletion of the Williams-Beuren syndrome interval implicates genes associated with defective visuospatial processing and autism.
abstract: BACKGROUND
  During a genetic study of autism, a female child who met diagnostic criteria for autism spectrum disorder, but also exhibited the cognitive-behavioural profile (CBP) associated with Williams-Beuren syndrome (WBS) was examined. The WBS CBP includes impaired visuospatial ability, an overly friendly personality, excessive non-social anxiety and language delay.
  
  
  METHODS
  Using array-based comparative genomic hybridisation (aCGH), a deletion corresponding to BAC RP11-89A20 in the distal end of the WBS deletion interval was detected. Hemizygosity was confirmed using fluorescence in situ hybridisation and fine mapping was performed by measuring the copy number of genomic DNA using quantitative polymerase chain reaction.
  
  
  RESULTS
  The proximal breakpoint was mapped to intron 1 of GTF2IRD1 and the distal breakpoint lies 2.4-3.1 Mb towards the telomere. The subject was completely hemizygous for GTF2I, commonly deleted in carriers of the classic approximately 1.5 Mb WBS deletion, and GTF2IRD2, deleted in carriers of the rare approximately 1.84 Mb WBS deletion.
  
  
  CONCLUSIONS
  Hemizygosity of the GTF2 family of transcription factors is sufficient to produce many aspects of the WBS CBP, and particularly implicate the GTF2 transcription factors in the visuospatial construction deficit. Symptoms of autism in this case may be due to deletion of additional genes outside the typical WBS interval or remote effects on gene expression at other loci.
authors.forename: Lisa
authors.initials: L
authors.lastname: Edelmann
authors.forename: Aaron
authors.initials: A
authors.lastname: Prosnitz
authors.forename: Sherly
authors.initials: S
authors.lastname: Pardo
authors.forename: Jahnavi
authors.initials: J
authors.lastname: Bhatt
authors.forename: Ninette
authors.initials: N
authors.lastname: Cohen
authors.forename: Tara
authors.initials: T
authors.lastname: Lauriat
authors.forename: Leonid
authors.initials: L
authors.lastname: Ouchanov
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: González
authors.forename: Elina R
authors.initials: ER
authors.lastname: Manghi
authors.forename: Pamela
authors.initials: P
authors.lastname: Bondy
authors.forename: Marcela
authors.initials: M
authors.lastname: Esquivel
authors.forename: Silvia
authors.initials: S
authors.lastname: Monge
authors.forename: Marietha F
authors.initials: MF
authors.lastname: Delgado
authors.forename: Alessandra
authors.initials: A
authors.lastname: Splendore
authors.forename: Uta
authors.initials: U
authors.lastname: Francke
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Burton
authors.forename: L Alison
authors.initials: LA
authors.lastname: McInnes
mesh_terms: D000377:Agnosia / Q000235:genetics*; D001321:Autistic Disorder / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7; D005260:Female; D006801:Humans; D007438:Introns; D017384:Sequence Deletion; D019473:Transcription Factors, TFII / Q000235:genetics; D018980:Williams Syndrome / Q000235:genetics*
chemical_list: C104259:GTF2I protein, human; D019473:Transcription Factors, TFII