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Genetic linkage analysis of the X chromosome in autism, with emphasis on the fragile X region

Vincent, John B.a d; Melmer, Georga; Bolton, Patrick F.b; Hodgkinson, Stevea; Holmes, Debbiea; Curtis, Davidc; Gurling, Hugh M.D.a

Original Articles

The higher prevalence of autism in males than in females suggests the possible involvement of the X chromosome. To test the hypothesis that there are mutations increasing susceptibility to autism on the X chromosome, and in particular the distal portion of the long arm that encompasses the FMRI and MECP2 loci, a genetic linkage study was performed. Twenty-two fragile X-negative families multiplex for autism and related disorders were used for the study. Linkage analysis, for markers in the Xq27–q28 region, using model-free likelihood-based analysis, produced a maximum MLOD of 1.7 for the narrowest diagnostic category of the typical autism/severe autism spectrum, and nonparametric analysis produced a maximum non-parametric lod (NPL) score of 2.1 for a broad phenotype diagnostic model. Thus, this study offers modest support for a susceptibility locus for autism within the Xq27–q28 region. Further genetic investigations of this region are warranted.

aMolecular Psychiatry Laboratory, Department of Psychiatry and Behavioural Sciences, Windeyer Institute of Medical Science, University College London, London

bDepartment of Developmental Psychiatry, University of Cambridge, Cambridge, UK

cRoyal London Hospital, London, UK

dNeurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canda

Sponsorship: The molecular genetic aspects of this research were funded by the Bethlem Royal and Maudsley Hospital Research Fund, The Wellcome Trust, with a senior fellowship in clinical science to H.M.D.G., and a research fellowship from Merck Sharp and Dohme to G.M. The clinical aspects of the project were supported by the Medical Research Council and the John D. and Catharine T. MacArthur Foundation grants to Michael Rutter and support for the collaboration with colleagues in Canada from grants to Catherine Lord from The Alberta Heritage Foundation for Medical Research and the Medical Research Council of Canada.

Correspondence and requests for reprints to John B. Vincent, Ph.D., R30, Neurogenetics Section, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ont., Canada M5T 1R8

Tel: +416 535 8501 ext. 6487; fax: +416 979 4666;


© 2005 Lippincott Williams & Wilkins, Inc.