The role of sex hormones in human language development

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.

Normative data stratified by three levels of age (16-59, 60-79, and 80-95 years) and three levels of education (0-8, 9-12, and 13-21 years) are presented for phonemic verbal fluency (FAS) and categorical verbal fluency (Animal Naming). The normative sample, aged 16 to 95 years, consisted of 1,300 cognitively intact individuals who resided in the community. Years of education ranged from 0 to 21. The total number of words in 1 minute for each of the letters F, A, and S was correlated r =.52 with the number of animal names generated in 1 minute. Regression analyses showed that FAS was more sensitive to the effects of education (18.6% of the variance) than age (11.0% of the variance). The opposite relationship occurred for Animal Naming, where age accounted for 23.4% of the variance and education accounted only for 13.6%. Gender accounted for less than 1% of variance for FAS and Animal Naming. The clinical utility of these norms is discussed.

Language is a uniquely human trait likely to have been a prerequisite for the development of human culture. The ability to develop articulate speech relies on capabilities, such as fine control of the larynx and mouth, that are absent in chimpanzees and other great apes. FOXP2 is the first gene relevant to the human ability to develop language. A point mutation in FOXP2 co-segregates with a disorder in a family in which half of the members have severe articulation difficulties accompanied by linguistic and grammatical impairment. This gene is disrupted by translocation in an unrelated individual who has a similar disorder. Thus, two functional copies of FOXP2 seem to be required for acquisition of normal spoken language. We sequenced the complementary DNAs that encode the FOXP2 protein in the chimpanzee, gorilla, orang-utan, rhesus macaque and mouse, and compared them with the human cDNA. We also investigated intraspecific variation of the human FOXP2 gene. Here we show that human FOXP2 contains changes in amino-acid coding and a pattern of nucleotide polymorphism, which strongly suggest that this gene has been the target of selection during recent human evolution.