title: Identification of a CACNA2D4 deletion in late onset bipolar disorder patients and implications for the involvement of voltage-dependent calcium channels in psychiatric disorders.
abstract: The GWAS-based association of CACNA1C with bipolar disorder (BPD) is one of the strongest genetic findings to date. CACNA1C belongs to the family of CACN genes encoding voltage-dependent calcium channels (VDCCs). VDCCs are involved in brain circuits and cognitive processes implicated in BPD and schizophrenia (SZ). Recently, it was shown that rare copy number variations (CNVs) are found at an increased frequency in SZ and to a lesser extent also in BPD, suggesting the involvement of CNVs in the causation of these diseases. We hypothesize that CNVs in CACN genes can influence the susceptibility to BPD, SZ, and/or schizoaffective disorder (SZA). A search for CNVs in eight CACN genes in a patient-control sample of European decent was performed. A total of 709 BP patients, 645 SZ patients, 189 SZA patients, and 1,470 control individuals were screened using the Multiplex Amplicon Quantification (MAQ) method. We found a rare, partial deletion of 35.7 kb in CACNA2D4 in two unrelated late onset bipolar I patients and in one control individual. All three deletions shared the same breakpoints removing exons 17-26 of CACNA2D4, comprising part of the CACHE domain. Based on the data we cannot claim causality to BPD of the identified CACNA2D4 deletion but nevertheless this deletion can be important in unraveling the underlying processes leading to psychiatric diseases in general and BPD in particular.
authors.affiliation: Applied Molecular Genomics Group, VIB Department of Molecular Genetics, VIB, Antwerp, Belgium.
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Van Den Bossche
authors.forename: Mojca
authors.initials: M
authors.lastname: Strazisar
authors.forename: Stephan
authors.initials: S
authors.lastname: De Bruyne
authors.forename: Chris
authors.initials: C
authors.lastname: Bervoets
authors.forename: An-Sofie
authors.initials: AS
authors.lastname: Lenaerts
authors.forename: Sonia
authors.initials: S
authors.lastname: De Zutter
authors.forename: Annelie
authors.initials: A
authors.lastname: Nordin
authors.forename: Karl-Fredrik
authors.initials: KF
authors.lastname: Norrback
authors.forename: Dirk
authors.initials: D
authors.lastname: Goossens
authors.forename: Peter
authors.initials: P
authors.lastname: De Rijk
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Green
authors.forename: Detelina
authors.initials: D
authors.lastname: Grozeva
authors.forename: Julien
authors.initials: J
authors.lastname: Mendlewicz
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
authors.forename: Bernard G
authors.initials: BG
authors.lastname: Sabbe
authors.forename: Rolf
authors.initials: R
authors.lastname: Adolfsson
authors.forename: Daniel
authors.initials: D
authors.lastname: Souery
authors.forename: Jurgen
authors.initials: J
authors.lastname: Del-Favero
mesh_terms: D000328:Adult; D017668:Age of Onset; D020029:Base Pairing / Q000235:genetics; D001530:Belgium / Q000453:epidemiology; D001714:Bipolar Disorder / Q000453:epidemiology* / Q000235:genetics*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology
chemical_list: C498838:CACNA2D4 protein, human; D020746:Calcium Channels, L-Type