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N Engl J Med. 2008 Nov 27;359(22):2337-45. doi: 10.1056/NEJMoa0802828. Epub 2008 Nov 5.

A functional genetic link between distinct developmental language disorders.

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  • 1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.

Abstract

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.

2008 Massachusetts Medical Society

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PMID:
18987363
[PubMed - indexed for MEDLINE]
PMCID:
PMC2756409
Free PMC Article

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