title: Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization.
abstract: OBJECTIVE
  The goal of this study was to identify new candidate genes and genomic copy-number variations associated with a rare, severe, and persistent speech disorder termed childhood apraxia of speech. Childhood apraxia of speech is the speech disorder segregating with a mutation in FOXP2 in a multigenerational London pedigree widely studied for its role in the development of speech-language in humans.
  
  
  METHODS
  A total of 24 participants who were suspected to have childhood apraxia of speech were assessed using a comprehensive protocol that samples speech in challenging contexts. All participants met clinical-research criteria for childhood apraxia of speech. Array comparative genomic hybridization analyses were completed using a customized 385K Nimblegen array (Roche Nimblegen, Madison, WI) with increased coverage of genes and regions previously associated with childhood apraxia of speech.
  
  
  RESULTS
  A total of 16 copy-number variations with potential consequences for speech-language development were detected in 12 or half of the 24 participants. The copy-number variations occurred on 10 chromosomes, 3 of which had two to four candidate regions. Several participants were identified with copy-number variations in two to three regions. In addition, one participant had a heterozygous FOXP2 mutation and a copy-number variation on chromosome 2, and one participant had a 16p11.2 microdeletion and copy-number variations on chromosomes 13 and 14.
  
  
  CONCLUSIONS
  Findings support the likelihood of heterogeneous genomic pathways associated with childhood apraxia of speech.
authors: University of Wisconsin-Madison, USA.
authors: Jennifer J S
authors: JJ
authors: Laffin
authors: Gordana
authors: G
authors: Raca
authors: Craig A
authors: CA
authors: Jackson
authors: Edythe A
authors: EA
authors: Strand
authors: Kathy J
authors: KJ
authors: Jakielski
authors: Lawrence D
authors: LD
authors: Shriberg
mesh_terms: D000293:Adolescent; D001072:Apraxias / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002877:Chromosomes, Human / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods*; D056915:DNA Copy Number Variations; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D013064:Speech Disorders / Q000175:diagnosis / Q000235:genetics*
chemical_list: C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors