SCN8A encephalopathy: Research progress and prospects.
SCN8A encephalopathy: Research progress and prospects.
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DOI：
10.1111/epi.13422
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发表时间：
2016-07
期刊：
影响因子：
5.6
通讯作者：
Scheffer IE
中科院分区：
文献类型：
--
作者：
Meisler MH;Helman G;Hammer MF;Fureman BE;Gaillard WD;Goldin AL;Hirose S;Ishii A;Kroner BL;Lossin C;Mefford HC;Parent JM;Patel M;Schreiber J;Stewart R;Whittemore V;Wilcox K;Wagnon JL;Pearl PL;Vanderver A;Scheffer IE
2015年4月21日，首个SCN8A脑病研究小组在华盛顿特区召开会议，评估该疾病临床和致病特征的当前研究，并为未来的研究合作准备议程。该小组由临床和基础科学家以及患者倡导团体的代表组成。SCN8A脑病是由编码神经元钠通道Nav1.6的钠通道基因SCN8A重新错义突变引起的一种罕见疾病。自2012年首次描述以来，在出版物或SCN8A家族群体中报告了大约140名受影响的个体。因此，对SCN8A突变的严重影响的理解开始出现。定义遗传性癫痫综合征超越了分子病因学的鉴定。本次会议讨论的主题包括(1)Dravet综合征中SCN8A和SCN1A突变的比较，(2)Nav1.6通道的生物物理特性，(3)患者突变对通道特性的电生理影响，(4)SCN8A脑病的细胞和动物模型，(5)药物筛选策略，(6)SCN8A脑病的表型谱，以及(7)发展生物登记的努力。小组讨论了生物登记、生物银行和临床结果数据方面的差距，随后是改善临床和基础科学研究整合的规划会议。虽然最近才发现SCN8A脑病，但在功能分析和表型分类方面进展迅速。现在的重点正在从确定潜在的分子原因转移到制定药物筛选和优先患者护理的策略。
On April 21, 2015, the first SCN8A Encephalopathy Research Group convened in Washington, DC, to assess current research into clinical and pathogenic features of the disorder and prepare an agenda for future research collaborations. The group comprised clinical and basic scientists and representatives of patient advocacy groups. SCN8A encephalopathy is a rare disorder caused by de novo missense mutations of the sodium channel gene SCN8A, which encodes the neuronal sodium channel Nav1.6. Since the initial description in 2012, approximately 140 affected individuals have been reported in publications or by SCN8A family groups. As a result, an understanding of the severe impact of SCN8A mutations is beginning to emerge. Defining a genetic epilepsy syndrome goes beyond identification of molecular etiology. Topics discussed at this meeting included (1) comparison between mutations of SCN8A and the SCN1A mutations in Dravet syndrome, (2) biophysical properties of the Nav1.6 channel, (3) electrophysiologic effects of patient mutations on channel properties, (4) cell and animal models of SCN8A encephalopathy, (5) drug screening strategies, (6) the phenotypic spectrum of SCN8A encephalopathy, and (7) efforts to develop a bioregistry. A panel discussion of gaps in bioregistry, biobanking, and clinical outcomes data was followed by a planning session for improved integration of clinical and basic science research. Although SCN8A encephalopathy was identified only recently, there has been rapid progress in functional analysis and phenotypic classification. The focus is now shifting from identification of the underlying molecular cause to the development of strategies for drug screening and prioritized patient care.