1. ¹The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
2. ²Department of Molecular Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany
3. ³Department of Child and Adolescent Psychiatry, University of Frankfurt, Frankfurt, Germany
4. ⁴University of Bologna, Dipartimento di Biologia Evoluzionistica Sperimentale and Lab Genetica Medica, Policlinico S. Orsola-Malpighi, Bologna, Italy
5. ⁵Stella Maris Clinical Research Institute for Child and Adolescent Neuropsychiatry, Calambrone, Italy
6. ⁶Videnscenter Og Centre for Autisme, Virum, Denmark
7. ⁷Borne-Og Ungdomspsykiatrisk Hospital, Risskov, Denmark
8. ⁸John Kennedy Instituttet, Glostrup, Denmark
9. ⁹Biophysics Group, Danish Technical University, Lyngby, Denmark
10. ¹⁰Department of Child and Adolescent Psychiatry, Utrecht, Netherlands
11. ¹¹Centre for Social, Genetic and Developmental Psychiatry and Department of Child and Adolescent Psychiatry, Institute of Psychiatry, London
12. ¹²Section of Child and Adolescent Psychiatry, Park Hospital for Children, Oxford, UK
13. ¹³http://www.well.ox.ac.uk/~maes
    trin/iat.html

Correspondence: Professor AP Monaco, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. Tel: +44 1865 287502; Fax: +44 1865 287650; E-mail: anthony.monaco@well.ox.ac.uk; AJ Bailey, Section of Child and Adolescent Psychiatry, University of Oxford, Park Hospital for Children, Old Road, Headington, Oxford, OX3 7LQ, UK. Tel: +44 1865 226517; Fax: +44 1865 762358; E-mail: anthony.bailey@psychiatry.oxford.ac.uk

¹⁴Current address: Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA

Received 17 May 2004; Revised 31 August 2004; Accepted 7 September 2004; Published online 3 November 2004.

Abstract

Genetic studies have provided evidence for an autism susceptibility locus (AUTS1) on chromosome 7q. Screening for mutations in six genes mapping to 7q, CUTL1, SRPK2, SYPL, LAMB1, NRCAM and PTPRZ1 in 48 unrelated individuals with autism led to the identification of several new coding variants in the genes CUTL1, LAMB1 and PTPRZ1. Analysis of genetic variants provided evidence for association with autism for one of the new missense changes identified in LAMB1; this effect was stronger in a subgroup of affected male sibling pair families, implying a possible specific sex-related effect for this variant. Association was also detected for several polymorphisms in the promoter and untranslated region of NRCAM, suggesting that alterations in expression of this gene may be linked to autism susceptibility.