Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Localisation of a gene implicated in a severe speech and language disorder

A Correction to this article was published on 01 March 1998


Between 2 and 5% of children who are otherwise unimpaired have significant difficulties in acquiring expressive and/or receptive language, despite adequate intelligence and opportunity1,2. While twin studies indicate a significant role for genetic factors in developmental disorders of speech and language1, the majority of families segregating such disorders show complex patterns of inheritance, and are thus not amenable for conventional linkage analysis2. A rare exception is the KE family, a large three-generation pedigree in which approximately half of the members are affected with a severe speech and language disorder which appears to be transmitted as an autosomal dominant monogenic trait3. This family has been widely publicised as suffering primarily from a defect in the use of grammatical suffixa-tion rules4–7, thus supposedly supporting the existence of genes specific to grammar. The phenotype, however, is broader in nature, with virtually every aspect of grammar and of language affected8–10. In addition, affected members have a severe orofa-cial dyspraxia, and their speech is largely incomprehensible to the naive listener10. We initiated a genome-wide search for linkage in the KE family and have identified a region on chromosome 7 which co-segregates with the speech and language disorder (maximum lod score = 6.62 at θ = 0.0), confirming autosomal dominant inheritance with full penetrance. Further analysis of microsatellites from within the region enabled us to fine map the locus responsible (designated SPCH1) to a 5.6-cM interval in 7q31, thus providing an important step towards its identification. Isolation of SPCH1 may offer the first insight into the molecular genetics of the developmental process that culminates in speech and language.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others


  1. Bishop, D.V.M., North, T. & Donlan, C. Genetic basis of specific language impairment: evidence from a twin study. Dev. Med. Child Neurol. 37, 56–71 (1995).

    Article  CAS  Google Scholar 

  2. Smith, S.D., Gilger, J.W. & Pennington, B.F. Dyslexia and other specific learning disorders, in Principles and Practice of Medical Genetics (eds. D.L. Rimoin, J.M. Connor & R.E. Pyeritz) 1767–1789 (Churchill Livingston, New York, 1996).

  3. Hurst, J.A., Baraitser, M., Auger, E., Graham, F. & Norell, S. An extended family with a dominantly inherited speech disorder. Dev. Med. Child Neurol. 32, 347–355 (1990).

    Google Scholar 

  4. Gopnik, M. Feature-blind grammar and dysphasia. Nature 344, 715 (1990).

    Article  CAS  Google Scholar 

  5. Gopnik, M. & Crago, M.B. Familial aggregation of a developmental language disorder. Cognition 39, 1–50 (1991).

    Article  CAS  Google Scholar 

  6. Pinker, S. Rules of language. Science 253, 530–535 (1991).

    Article  CAS  Google Scholar 

  7. Pinker, S. The Language Instinct. (Alien Lane, London, 1994).

  8. Fletcher, P. Speech and language defects. Nature 346, 226 (1990).

    Article  Google Scholar 

  9. Vargha-Khadem, F. & Passingham, R.E. Speech and laguage defects. Nature 346, 226 (1990).

    Article  Google Scholar 

  10. Vargha-Khadem, F., Watkins, K., Alcock, K., Fletcher, P. & Passingham, R. Praxic and nonverbal cognitive deficits in a large family with a genetically transmitted speech and language disorder. Proc. Natal. Acad. Sci. USA 92, 930–933 (1995).

    Article  CAS  Google Scholar 

  11. Maynard Smith, J. & Szathmary, E. The Major Transitions in Evolution. (W.H. Freeman, Oxford, 1995).

  12. Reed, P.W. et al. Chromosome-specific microsatellite sets for fluorescence-based, semi-automated genome mapping. Nature Genet. 7, 390–395 (1994).

    Article  CAS  Google Scholar 

  13. Dib, C. et al. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature 380, 152–154 (1996).

    Article  CAS  Google Scholar 

  14. Schuler, G.D. et al. A gene map of the human genome. Science 274, 540–546 (1996).

    Article  CAS  Google Scholar 

  15. Bouffard, G.G. et al. A physical map of human chromosome 7: an integrated YAC contig map with average STS spacing of 79 kb. Genome Res. 7, 673–692 (1997).

    Article  CAS  Google Scholar 

  16. Schinzel, A. Human Genetics Database. (Oxford University Press, Oxford, 1997).

  17. Sarda, P., Turleau, C., Cabanis, M.-O., Jalaguier, J., de Grouchy, J. & Bonnet, H. Interstitial deletion in the long arm of chromosome 7. Ann. Genet. 31, 258–261 (1988).

    CAS  PubMed  Google Scholar 

  18. The international Molecular Genetic Study of Autism Consortium. A full genome screen for autism with evidence for linkage to a region on chromosome 7q. Hum. Mol. Genet (in press).

  19. Lathrop, G.M., Lalouel, J.-M., Julier, C. & Ott, J. Strategies for multilocus linkage analysis in humans. Proc. Natal. Acad. Sci. USA 81, 3443–3446 (1984).

    Article  CAS  Google Scholar 

  20. O'Connell, J.R. & Weeks, D.E. The VITESSE algorithm for rapid exact multilocus linkage analysis via genotype set-recording and fuzzy inheritance. Nature Genet. 11, 402–408 (1995).

    Article  CAS  Google Scholar 

  21. Sobel, E. & Lange, K. Descent graphs in pedigree analysis: applications to haplotyping, location scores and marker sharing statistics. Am. J. Hum. Genet. 58, 1323–1337 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Anthony P. Monaco.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fisher, S., Vargha-Khadem, F., Watkins, K. et al. Localisation of a gene implicated in a severe speech and language disorder. Nat Genet 18, 168–170 (1998).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing