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Letters to Nature

Nature 413, 519-523 (4 October 2001) | doi:10.1038/35097076; Received 13 February 2001; Accepted 27 July 2001

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

Cecilia S. L. Lai1,4, Simon E. Fisher1,4, Jane A. Hurst2, Faraneh Vargha-Khadem3 & Anthony P. Monaco1

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
  2. Department of Clinical Genetics, Oxford Radcliffe Hospital, Oxford OX3 7LJ, UK
  3. Developmental Cognitive Neuroscience Unit, Institute of Child Health, Mecklenburgh Square, London WC1N 2AP, UK
  4. These authors contributed equally to this work

Correspondence to: Anthony P. Monaco1 Correspondence and requests for materials should be addressed to A.P.M. (e-mail: Email: anthony@well.ox.ac.uk).

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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 opportunity1. Although studies of twins consistently indicate that a significant genetic component is involved1, 2, 3, most families segregating speech and language deficits show complex patterns of inheritance, and a gene that predisposes individuals to such disorders has not been identified. We have studied a unique three-generation pedigree, KE, in which a severe speech and language disorder is transmitted as an autosomal-dominant monogenic trait4. Our previous work mapped the locus responsible, SPCH1, to a 5.6-cM interval of region 7q31 on chromosome 7 (ref. 5). We also identified an unrelated individual, CS, in whom speech and language impairment is associated with a chromosomal translocation involving the SPCH1 interval6. 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. In addition, we identify a point mutation in affected members of the KE family that alters an invariant amino-acid residue in the forkhead domain. Our findings suggest that FOXP2 is involved in the developmental process that culminates in speech and language.

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
  2. Department of Clinical Genetics, Oxford Radcliffe Hospital, Oxford OX3 7LJ, UK
  3. Developmental Cognitive Neuroscience Unit, Institute of Child Health, Mecklenburgh Square, London WC1N 2AP, UK
  4. These authors contributed equally to this work

Correspondence to: Anthony P. Monaco1 Correspondence and requests for materials should be addressed to A.P.M. (e-mail: Email: anthony@well.ox.ac.uk).