A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-associated common SNP of CACNA1C in brain.
A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-associated common SNP of CACNA1C in brain.
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DOI：
10.1038/mp.2013.107
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发表时间：
2014-08
影响因子：
11
通讯作者：
Liu, C.
中科院分区：
文献类型：
--
作者：
Gershon, E. S.;Grennan, K.;Busnello, J.;Badner, J. A.;Ovsiew, F.;Memon, S.;Alliey-Rodriguez, N.;Cooper, J.;Romanos, B.;Liu, C.
Timothy综合征(TS)是由CACNA1C基因罕见的外显子突变引起的，在细胞动作电位过程中，CACNA1C基因的外显子突变会导致Cav1.2电压门控钙通道的延迟失活，导致钙离子大量流入激活的细胞。这种综合征的主要临床特征是QT间期延长，导致心律失常。然而，TS也包括认知障碍、自闭症和许多患者的主要发育迟缓。我们观察了一位先前报告的TS患者的双相情感障碍(BD)的表现，他是极少数存活到童年的患者之一。这是最有趣的，因为与BD关联最高的常见SNP是rs1006737，我们在这里显示了CACNA1C在人类小脑中的顺式表达数量性状基因座(EQTL)，而风险等位基因(A)与表达降低相关。将这位患者和具有常见CACNA1C SNP风险等位基因的患者合并存在BD时的CACNA1C扰动，我们认为可兴奋细胞中钙内流的增加或减少都与BD有关。在使用钙通道阻滞剂(CCB)治疗BD时，我们预测没有危险等位基因的患者会有更好的反应，因为他们增加了CACNA1C的表达。
Timothy Syndrome (TS) is caused by very rare exonic mutations of the CACNA1C gene that produce delayed inactivation of Cav1.2voltage-gated calcium channels during cellular action potentials, with greatly increased influx of calcium into the activated cells. The major clinical feature of this syndrome is a long QT interval that results in cardiac arrhythmias. However, TS also includes cognitive impairment, autism, and major developmental delays in many of the patients. We observed the appearance of Bipolar Disorder (BD) in a patient with a previously reported case of TS, who is one of the very few patients to survive childhood. This is most interesting because the common SNP most highly associated with BD is rs1006737, which we show here is a cis-expression quantitative trait locus (eQTL) for CACNA1C in human cerebellum, and the risk allele (A) is associated with decreased expression. To combine the CACNA1C perturbations in the presence of BD in this patient and in patients with the common CACNA1C SNP risk allele, we would propose that either increase or decrease in calcium influx in excitable cells can be associated with BD. In treatment of BD with calcium channel blocking drugs (CCBs), we would predict better response in patients without the risk allele, because they have increased CACNA1C expression.
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影响因子：
15.9
作者：
Nakayama, Hiroyuki;Chen, Xiongwen;Molkentin, Jeffery D.
通讯作者：
Molkentin, Jeffery D.
影响因子：
2.1
作者：
Bremer, T;Man, A;Diamond, C
通讯作者：
Diamond, C
影响因子：
3.3
作者：
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通讯作者：
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DOI：
10.1073/pnas.1112667108
发表时间：
2011-09-13
影响因子：
11.1
作者：
Bader, Patrick L.;Faizi, Mehrdad;Shamloo, Mehrdad
通讯作者：
Shamloo, Mehrdad
DOI：
10.1073/pnas.0511322103
发表时间：
2006-03-07
影响因子：
11.1
作者：
Erxleben, C;Liao, YH;Armstrong, DL
通讯作者：
Armstrong, DL