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.
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Acknowledgements
We thank R van't Slot, E Strengman and D Lugtenberg for their technical support. This work was supported by grants from the Netherlands Organization for Health Research and Development (to JAV, ZonMW 912-04-047 and 917-66-363) and Grant P50 MH 66392-01 awarded by the NIMH to Kenneth Davis.
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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)
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Friedman, J., Vrijenhoek, T., Markx, S. et al. CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy. Mol Psychiatry 13, 261–266 (2008). https://doi.org/10.1038/sj.mp.4002049
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DOI: https://doi.org/10.1038/sj.mp.4002049
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