1. ¹Department of Medical Genetics, Wilhelm Johannsen Centre for Functional Genome Research, Institute of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen N, Denmark
2. ²Centre for Psychiatric Research, Aarhus University Hospital, Riskov, Denmark
3. ³NANEA, Department of Epidemiology, Institute of Public Health, University of Aarhus, Aarhus, Denmark
4. ⁴Department of Medical Anatomy, University of Copenhagen, Copenhagen N, Denmark
5. ⁵Instituto Gulbenkian de Ciência, Oeiras, Portugal
6. ⁶Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal
7. ⁷Hospital Pediátrico de Coimbra, Coimbra, Portugal
8. ⁸Psychiatric Hospital, Hillerød, Denmark
9. ⁹Department of Medical Genetics, Institute of Molecular and Cellular Medicine, University of Copenhagen, Copenhagen N, Denmark
10. ¹⁰Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen S, Denmark
11. ¹¹Kennedy Institute – National Eye Clinic, Glostrup, Denmark
12. ¹²Biophysics Group, Department of physics, Danish Technical University, Lyngby, Denmark
13. ¹³Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark
14. ¹⁴Max-Planck Institute for Molecular Genetics, Berlin, Germany

Correspondence: Dr M Gilling, Wilhelm Johannsen Centre for Functional Genome Research, Department of Medical Genetics, Institute of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, Copenhagen N 2200, Denmark. Tel: +45 35327846; Fax: +45 35327845; E-mail: mette@imbg.ku.dk

¹⁵Claes Lundsteen died on 10 November 2003.

Received 17 August 2007; Revised 23 October 2007; Accepted 20 November 2007; Published online 9 January 2008.

Abstract

Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with unknown aetiology. Even though ASDs are suggested to be among the most heritable complex disorders, only a few reproducible mutations leading to susceptibility for ASD have been identified. In an attempt to identify ASD susceptibility genes through chromosome rearrangements, we investigated a female patient with childhood autism and high-grade myopia, and an apparently balanced de novo translocation, t(5;18)(q34;q12.2). Further analyses revealed a 3.2 Mb deletion encompassing 17 genes at the 18q break point and an additional deletion of 1.27 Mb containing two genes on chromosome 4q35. Q-PCR analysis of 14 of the 17 genes deleted on chromosome 18 showed that 11 of these genes were expressed in the brain, suggesting that haploinsufficiency of one or more genes may have contributed to the childhood autism phenotype of the patient. Identification of multiple genetic changes in this patient with childhood autism agrees with the most frequently suggested genetic model of ASDs as complex, polygenic disorders.