A forkhead-domain gene is mutated in a severe speech and language disorder

@article{Lai2001AFG,
  title={A forkhead-domain gene is mutated in a severe speech and language disorder},
  author={Cecilia S. L. Lai and Simon E. Fisher and Jane A. Hurst and Faraneh Vargha-Khadem and Anthony P. Monaco},
  journal={Nature},
  year={2001},
  volume={413},
  pages={519-523}
}
Individuals affected with developmental disorders of speech and language have substantial difficulty acquiring expressive and/or receptive language in the absence of any profound sensory or neurological impairment and despite adequate intelligence and opportunity. [] Key Result Here we show that the gene FOXP2, which encodes a putative transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain, is directly disrupted by the translocation breakpoint in CS.
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Functional genetic analysis of mutations implicated in a human speech and language disorder.

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Mutation screening of FOXP2 in the KE family revealed a point mutation in all affected individuals, which leads to alteration of a key residue in the DNA-binding domain, and is predicted to disrupt the func­tion of the protein.

Deciphering the genetic basis of speech and language disorders.

Investigation of a unique three-generation family showing monogenic inheritance of speech and language deficits led to the isolation of the first such gene on chromosome 7, which encodes a transcription factor known as FOXP2.

Genetics of speech and language disorders.

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The discovery of mutations in the FOXP2 gene led to a new avenue of investigation into the substrates and mechanisms that underlie human speech development, and linkage studies have identified several loci, and candidate gene association studies are making progress in identifying causal variants at these loci.

A functional genetic link between distinct developmental language disorders.

The FOXP2-CNTNAP2 pathway provides a mechanistic link between clinically distinct syndromes involving disrupted language, and is found to be associated with language delays in children with autism.

The speech gene FOXP2 is not imprinted

The Forkhead-box protein P2 ( FOXP2 ) was the first gene to be linked to an inherited form of speech and language disorder, described as developmental verbal dyspraxia (DVD), and findings have been described as evidence supporting a theoretical role for imprinting in the evolution of language.

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

Investigation of the entire coding region of FOXP2, including alternatively spliced exons, in 49 probands affected with verbal dyspraxia and the discovery of the first nonsense mutation in FoxP2 opens the door for detailed investigations of neurodevelopment in people carrying different etiological variants of the gene.

FOXP2 is not a major susceptibility gene for autism or specific language impairment.

It is concluded that coding-region variants in FOXP2 do not underlie the AUTS1 linkage and that the gene is unlikely to play a role in autism or more common forms of language impairment.

Monogenic and chromosomal causes of isolated speech and language impairment

The clinical features, aetiology and management options of known chromosomal and single gene disorders that are associated with speech and language pathology in the setting of normal or only mildly impaired cognitive function are summarized.

FOXP2 variants in 14 individuals with developmental speech and language disorders broaden the mutational and clinical spectrum

By identifying intragenic deletions or mutations in 14 individuals from eight unrelated families with variable developmental delay/cognitive impairment and speech and language deficits, this work considerably broaden the mutational and clinical spectrum associated with aberrations in FOXP2.
...

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