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

Journal article

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. Although studies of twins consistently indicate that a significant genetic component is involved, 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 trait. 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 interval. 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.

Authors: Lai, C; Fisher, S; Hurst, J; Vargha-Khadem, F; Monaco, A

• Publication status: Published
• Journal: Nature More from this journal
• Volume: 413
• Issue: 6855
• Pages: 519-523
• Publication date: 2001-10-01
• DOI: 10.1038/35097076
• EISSN: 1476-4687
• ISSN: 0028-0836
• Language: English
• Keywords: Pedigree; Female; Translocation, Genetic; Point Mutation; Sequence Homology, Amino Acid; Forkhead Transcription Factors; Protein Structure, Tertiary; Transcription Factors; Amino Acid Sequence; Chromosome Mapping; Language Disorders; Speech Disorders; Repressor Proteins; Chromosomes, Human, Pair 7; Humans; Male; Molecular Sequence Data