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

Nature Genetics volume 18, pages 168170 (1998) | Download Citation



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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  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


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Correspondence to Anthony P. Monaco.

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