A functional genetic link between distinct developmental language disorders

Sonja C Vernes, Dianne F Newbury, Brett S Abrahams, Laura Winchester, Jérôme Nicod, Matthias Groszer, Maricela Alarcón, Peter L Oliver, Kay E Davies, Daniel H Geschwind, Anthony P Monaco, Simon E Fisher

Research output: Contribution to journalArticlepeer-review

459 Citations (Scopus)


BACKGROUND: Rare mutations affecting the FOXP2 transcription factor cause a monogenic speech and language disorder. We hypothesized that neural pathways downstream of FOXP2 influence more common phenotypes, such as specific language impairment.

METHODS: We performed genomic screening for regions bound by FOXP2 using chromatin immunoprecipitation, which led us to focus on one particular gene that was a strong candidate for involvement in language impairments. We then tested for associations between single-nucleotide polymorphisms (SNPs) in this gene and language deficits in a well-characterized set of 184 families affected with specific language impairment.

RESULTS: We found that FOXP2 binds to and dramatically down-regulates CNTNAP2, a gene that encodes a neurexin and is expressed in the developing human cortex. On analyzing CNTNAP2 polymorphisms in children with typical specific language impairment, we detected significant quantitative associations with nonsense-word repetition, a heritable behavioral marker of this disorder (peak association, P=5.0x10(-5) at SNP rs17236239). Intriguingly, this region coincides with one associated with language delays in children with autism.

CONCLUSIONS: The FOXP2-CNTNAP2 pathway provides a mechanistic link between clinically distinct syndromes involving disrupted language.

Original languageEnglish
Pages (from-to)2337-45
Number of pages9
JournalNew England Journal of Medicine
Issue number22
Publication statusPublished - 27 Nov 2008


  • Child
  • Chromatin Immunoprecipitation
  • Down-Regulation
  • Female
  • Forkhead Transcription Factors/genetics
  • Gene Expression Regulation
  • Genetic Markers
  • Genome-Wide Association Study
  • Haplotypes
  • Humans
  • Language Development Disorders/genetics
  • Male
  • Membrane Proteins/genetics
  • Nerve Tissue Proteins/genetics
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide


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