Localisation of a gene implicated in a severe speech and language disorder (original) (raw)

Nature Genetics volume 18, pages 168–170 (1998)Cite this article

A Correction to this article was published on 01 March 1998

Abstract

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.

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References

  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

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Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Windmill Road, Oxford, OX3 7BN, UK
    Simon E. Fisher & Anthony P. Monaco
  2. Cognitive Neuroscience Unit, Institute of Child Health, The Wolfson Centre, Mecklenburgh Square, London, WC1N2AP, UK
    Faraneh Vargha-Khadem & Kate E. Watkins
  3. Mothercare Unit of Clinical Genetics and Fetal Medicine, Institute of Child Health, 30 Guilford St., London, WC1N1EH, UK
    Marcus E. Pembrey

Authors

  1. Simon E. Fisher
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  2. Faraneh Vargha-Khadem
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  3. Kate E. Watkins
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  4. Anthony P. Monaco
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  5. Marcus E. Pembrey
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Correspondence toAnthony P. Monaco.

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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). https://doi.org/10.1038/ng0298-168

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