1. ¹Departments of Psychiatry and Human Genetics, Mount Sinai School of Medicine, New York, NY, USA
2. ²Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
3. ³Department of Psychiatry, Columbia University, New York, NY, USA
4. ⁴Department of Psychiatry, Utrecht University, Utrecht, The Netherlands
5. ⁵Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
6. ⁶Department of Medical Genetics, Utrecht University, Utrecht, The Netherlands
7. ⁷Department of Genetics, University Medical Centre Groningen, Groningen, The Netherlands

Correspondence: Dr JA Veltman, Department of Human Genetics, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Geert Grooteplein 10, PO Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: j.veltman@antrg.umcn.nl

⁸These authors contributed equally to this work.

Received 10 April 2007; Revised 14 June 2007; Accepted 27 June 2007; Published online 24 July 2007.

Abstract

A homozygous mutation of the CNTNAP2 gene has been associated with a syndrome of focal epilepsy, mental retardation, language regression and other neuropsychiatric problems in children of the Old Order Amish community. Here we report genomic rearrangements resulting in haploinsufficiency of the CNTNAP2 gene in association with epilepsy and schizophrenia. Genomic deletions of varying sizes affecting the CNTNAP2 gene were identified in three non-related Caucasian patients. In contrast, we did not observe any dosage variation for this gene in 512 healthy controls. Moreover, this genomic region has not been identified as showing large-scale copy number variation. Our data thus confirm an association of CNTNAP2 to epilepsy outside the Old Order Amish population and suggest that dosage alteration of this gene may lead to a complex phenotype of schizophrenia, epilepsy and cognitive impairment.