From jel@christa.unh.edu Wed Feb 25 07:25:23 1998
Date: Wed, 25 Feb 1998 07:18:21 -0500 (EST)
From: John E Limber 
To: jel@christa.unh.edu
Subject: v18n2.885244343.html


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                     Volume 18 Number 2 - February 1998
                                      
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   Localisation of a gene implicated in a severe speech and language
   disorder
   Simon E. Fisher1, Faraneh Vargha-Khadem2, Kate E. Watkins2, Anthony P.
   Monaco1 & Marcus E. Pembrey3
   
   1Wellcome Trust Centre for Human Genetics, University of Oxford,
   Windmill Road, Oxford, OX3 7BN, UK. 2Cognitive Neuroscience Unit,
   Institute of Child Health, The Wolfson Centre, Mecklenburgh Square,
   London, WC1N 2AP, UK. 3Mothercare Unit of Clinical Genetics and Fetal
   Medicine, Institute of Child Health, 30 Guilford St., London, WC1N
   1EH, UK. Correspondence should be addressed to A.P.M. e-mail:
   anthony.monaco@well.ox.ac.uk
   
     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 suffixation
     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 orofacial
     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 theta = 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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