Referenced in: none

Automatically associated channels: Cav1.2

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.

Authors: Maarten J Van Den Bossche, Mojca Strazisar, Stephan De Bruyne, Chris Bervoets, An-Sofie Lenaerts, Sonia De Zutter, Annelie Nordin, Karl-Fredrik Norrback, Dirk Goossens, Peter De Rijk, Elaine K Green, Detelina Grozeva, Julien Mendlewicz, Nick Craddock, Bernard G Sabbe, Rolf Adolfsson, Daniel Souery, Jurgen Del-Favero

Journal, date & volume: Am. J. Med. Genet. B Neuropsychiatr. Genet., 2012 Jun , 159B, 465-75

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22488967

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.