title: CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy.
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.
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: J I
authors.initials: JI
authors.lastname: Friedman
authors.forename: T
authors.initials: T
authors.lastname: Vrijenhoek
authors.forename: S
authors.initials: S
authors.lastname: Markx
authors.forename: I M
authors.initials: IM
authors.lastname: Janssen
authors.forename: W A
authors.initials: WA
authors.lastname: van der Vliet
authors.forename: B H W
authors.initials: BH
authors.lastname: Faas
authors.forename: N V
authors.initials: NV
authors.lastname: Knoers
authors.forename: W
authors.initials: W
authors.lastname: Cahn
authors.forename: R S
authors.initials: RS
authors.lastname: Kahn
authors.forename: L
authors.initials: L
authors.lastname: Edelmann
authors.forename: K L
authors.initials: KL
authors.lastname: Davis
authors.forename: J M
authors.initials: JM
authors.lastname: Silverman
authors.forename: H G
authors.initials: HG
authors.lastname: Brunner
authors.forename: A Geurts
authors.initials: AG
authors.lastname: van Kessel
authors.forename: C
authors.initials: C
authors.lastname: Wijmenga
authors.forename: R A
authors.initials: RA
authors.lastname: Ophoff
authors.forename: J A
authors.initials: JA
authors.lastname: Veltman
mesh_terms: D000328:Adult; D002897:Chromosomes, Human, Pair 7; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D017421:Sequence Analysis
chemical_list: C403049:CNTNAP2 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins