Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization

Genet Med. 2012 Nov;14(11):928-36. doi: 10.1038/gim.2012.72. Epub 2012 Jul 5.


Purpose: 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.

Conclusion: Findings support the likelihood of heterogeneous genomic pathways associated with childhood apraxia of speech.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Apraxias / diagnosis
  • Apraxias / genetics*
  • Child
  • Child, Preschool
  • Chromosome Deletion
  • Chromosomes, Human / genetics
  • Comparative Genomic Hybridization / methods*
  • DNA Copy Number Variations
  • Female
  • Forkhead Transcription Factors / genetics
  • Genetic Predisposition to Disease
  • Genome, Human*
  • Heterozygote
  • Humans
  • Male
  • Mutation
  • Speech Disorders / diagnosis
  • Speech Disorders / genetics*


  • FOXP2 protein, human
  • Forkhead Transcription Factors