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首页> 外文期刊>Circulation journal >Dynamic Change in ST-Segment and Spontaneous Occurrence of Ventricular Fibrillation in Brugada Syndrome With a Novel Nonsense Mutation in the SCN5A Gene During Long-Term Follow-up
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Dynamic Change in ST-Segment and Spontaneous Occurrence of Ventricular Fibrillation in Brugada Syndrome With a Novel Nonsense Mutation in the SCN5A Gene During Long-Term Follow-up

机译:长期随访期间Brugada综合征中ST段的动态变化和自发性心室颤动伴SCN5A基因的新型无意义突变

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摘要

A 67-year-old male underwent genetic testing under the diagnosis of Brugada syndrome because of recurrent ventricular fibrillation with coincident ST-segment elevation in either right precordial, inferior leads or both since the age of 55 years. Screening of gene mutations using denaturing high-performance liquid chromatogra-phy (DHPLC) and direct sequencing identified a novel nonsense mutation (R179X) of SCN5A in a heterozygous manner. The functional assay for the identified mutation, using a whole-cell patch clamp in the heterologous expression system, revealed that the nonsense mutation, located in the second transmembrane segment of the first domain (DI-S2) of the a-subunit, failed to synthesize the complete structure of the cardiac sodium channel, thus causing the non-functional channel. Coding effects by the gene mutation was altered during the 12-year follow-up, which might affect the clinical features of the patient through the ion channel density in the ventricle, dynamics of repolarization abnormality and conduction disturbance.
机译:一名自67岁的男性开始接受Brugada综合征的基因检测,原因是自55岁以来,反复发生心室纤颤,右心前区,下位导线或两者同时出现ST段抬高。使用变性高效液相色谱(DHPLC)和直接测序对基因突变进行筛选,以杂合的方式鉴定出SCN5A的新型无义突变(R179X)。使用异源表达系统中的全细胞膜片钳对鉴定出的突变进行功能分析,发现位于a亚基第一个结构域(DI-S2)的第二个跨膜片段中的无意义突变未能合成了心脏钠通道的完整结构,从而导致了无功能的通道。在12年的随访期间,基因突变产生的编码效应发生了改变,这可能通过心室中的离子通道密度,复极异常和传导障碍的动力学影响患者的临床特征。

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