Identification of aCACNA2D4deletion in late onset bipolar disorder patients and implications for the involvement of voltage-dependent calcium channels in psychiatric disorders

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Abstract

The GWAS-based association ofCACNA1Cwith bipolar disorder (BPD) is one of the strongest genetic findings to date.CACNA1Cbelongs to the family ofCACNgenes 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 inCACNgenes can influence the susceptibility to BPD, SZ, and/or schizoaffective disorder (SZA). A search for CNVs in eightCACNgenes 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 inCACNA2D4in two unrelated late onset bipolar I patients and in one control individual. All three deletions shared the same breakpoints removing exons 17–26 ofCACNA2D4, comprising part of the CACHE domain. Based on the data we cannot claim causality to BPD of the identifiedCACNA2D4deletion but nevertheless this deletion can be important in unraveling the underlying processes leading to psychiatric diseases in general and BPD in particular. © 2012 Wiley Periodicals, Inc.

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