Identification of a CACNA2D4 deletion in late onset bipolar disorder patients and implications for the involvement of voltage-dependent calcium channels in psychiatric disorders

Van Den Bossche, Maarten J., Strazisar, Mojca, De Bruyne, Stephan, Bervoets, Chris, Lenaerts, An-Sofie, De Zutter, Sonia, Nordin, Annelie, Norrback, Karl-Fredrik, Goossens, Dirk, De Rijk, Peter, Green, Elaine Karen, Grozeva, Detelina ORCID: https://orcid.org/0000-0003-3239-8415, Mendlewicz, Julien, Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610, Sabbe, Bernard G., Adolfsson, Rolf, Souery, Daniel and Del-Favero, Jurgen 2012. Identification of a CACNA2D4 deletion in late onset bipolar disorder patients and implications for the involvement of voltage-dependent calcium channels in psychiatric disorders. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 159B (4) , pp. 465-475. 10.1002/ajmg.b.32053

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	voltage-dependent calcium channel genes; copy number variation; bipolar disorder; schizophrenia; schizoaffective disorder
Publisher:	Wiley-Blackwell
ISSN:	1552-4841
Date of Acceptance:	21 March 2012
Last Modified:	21 Oct 2022 10:25
URI:	https://orca.cardiff.ac.uk/id/eprint/40115

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