Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits

Kay D MacDermot, Elena Bonora, Nuala Sykes, Anne-Marie Coupe, Cecilia S L Lai, Sonja C Vernes, Faraneh Vargha-Khadem, Fiona McKenzie, Robert L Smith, Anthony P Monaco, Simon E Fisher

Research output: Contribution to journalArticlepeer-review

297 Citations (Scopus)


FOXP2, the first gene to have been implicated in a developmental communication disorder, offers a unique entry point into neuromolecular mechanisms influencing human speech and language acquisition. In multiple members of the well-studied KE family, a heterozygous missense mutation in FOXP2 causes problems in sequencing muscle movements required for articulating speech (developmental verbal dyspraxia), accompanied by wider deficits in linguistic and grammatical processing. Chromosomal rearrangements involving this locus have also been identified. Analyses of FOXP2 coding sequence in typical forms of specific language impairment (SLI), autism, and dyslexia have not uncovered any etiological variants. However, no previous study has performed mutation screening of children with a primary diagnosis of verbal dyspraxia, the most overt feature of the disorder in affected members of the KE family. Here, we report investigations of the entire coding region of FOXP2, including alternatively spliced exons, in 49 probands affected with verbal dyspraxia. We detected variants that alter FOXP2 protein sequence in three probands. One such variant is a heterozygous nonsense mutation that yields a dramatically truncated protein product and cosegregates with speech and language difficulties in the proband, his affected sibling, and their mother. Our discovery of the first nonsense mutation in FOXP2 now opens the door for detailed investigations of neurodevelopment in people carrying different etiological variants of the gene. This endeavor will be crucial for gaining insight into the role of FOXP2 in human cognition.

Original languageEnglish
Pages (from-to)1074-80
Number of pages7
JournalAmerican Journal of Human Genetics
Issue number6
Publication statusPublished - Jun 2005


  • Alternative Splicing
  • Amino Acid Sequence
  • Base Sequence
  • Codon, Initiator
  • Codon, Nonsense
  • Codon, Terminator
  • DNA Mutational Analysis
  • Exons
  • Forkhead Transcription Factors
  • Genetic Variation
  • Heterozygote
  • Humans
  • Language Disorders/etiology
  • Molecular Sequence Data
  • Mothers
  • Pedigree
  • Protein Isoforms/chemistry
  • Protein Structure, Tertiary
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Siblings
  • Speech Disorders/etiology
  • Transcription Factors/chemistry


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