Genetic disruption of voltage-gated calcium channels in psychiatric and neurological disorders.
Genetic disruption of voltage-gated calcium channels in psychiatric and neurological disorders.
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DOI：
10.1016/j.pneurobio.2015.09.002
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发表时间：
2015-11
影响因子：
6.7
通讯作者：
Dolphin AC
中科院分区：
文献类型：
--
作者：
Heyes S;Pratt WS;Rees E;Dahimene S;Ferron L;Owen MJ;Dolphin AC
电压门控钙通道分类-基因与蛋白质。神经精神综合征的遗传学分析从GWA精神疾病研究中鉴定的钙通道基因。精神疾病中钙通道基因的罕见突变。CACNA 1C突变和多态性的病理生理学后遗症由其他电压门控钙通道基因的有害突变引起的单基因疾病。疾病中钙通道基因表达的变化。电压门控钙通道参与早期脑发育。这篇综述总结了遗传学研究中，钙通道基因已连接到频谱的神经精神综合征，从双相情感障碍和精神分裂症自闭症谱系障碍和智力障碍。在许多其他基因中，通过各种DNA分析技术，钙通道基因超家族的惊人数量与这些疾病的病因学有关。我们将讨论这些与钙通道点突变相关的已知单基因疾病的关系。然后，我们将检查这些突变或单核苷酸多态性和疾病过程之间的因果关系的功能证据。未来的一个主要挑战将是将不断扩大的精神病学遗传学发现转化为改变的生理功能，参与更广泛的疾病病理学，以及为患者提供个性化和分层治疗选择的潜力。
Voltage-gated calcium channel classification—genes and proteins. Genetic analysis of neuropsychiatric syndromes. Calcium channel genes identified from GWA studies of psychiatric disorders. Rare mutations in calcium channel genes in psychiatric disorders. Pathophysiological sequelae of CACNA1C mutations and polymorphisms. Monogenic disorders resulting from harmful mutations in other voltage-gated calcium channel genes. Changes in calcium channel gene expression in disease. Involvement of voltage-gated calcium channels in early brain development. This review summarises genetic studies in which calcium channel genes have been connected to the spectrum of neuropsychiatric syndromes, from bipolar disorder and schizophrenia to autism spectrum disorders and intellectual impairment. Among many other genes, striking numbers of the calcium channel gene superfamily have been implicated in the aetiology of these diseases by various DNA analysis techniques. We will discuss how these relate to the known monogenic disorders associated with point mutations in calcium channels. We will then examine the functional evidence for a causative link between these mutations or single nucleotide polymorphisms and the disease processes. A major challenge for the future will be to translate the expanding psychiatric genetic findings into altered physiological function, involvement in the wider pathology of the diseases, and what potential that provides for personalised and stratified treatment options for patients.