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

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Lai, C S; Fisher, S E; Hurst, J A; Vargha-Khadem, F; Monaco, A P
Year of Publication: 2001
Journal: Nature
Volume: 413
Issue: 6855
Pagination: 519-23
Date Published: 2001 Oct 4
Publication Language: eng
ISSN: 0028-0836
Keywords: Amino Acid Sequence, Chromosome Mapping, Chromosomes, Human, Pair 7, Female, Forkhead Transcription Factors, Humans, Language Disorders, Male, Molecular Sequence Data, Pedigree, Point Mutation, Protein Structure, Tertiary, Repressor Proteins, Sequence Homology, Amino Acid, Speech Disorders, Transcription Factors, Translocation, Genetic

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.

DOI: 10.1038/35097076
Alternate Journal: Nature
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