(分子遗传学的遗传形式长QT综合征)。

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Georgijevic Milic L

(分子遗传学的遗传形式长QT综合征)。

地中海Pregl。2000; 1 - 2月53 (1 - 2):51-4。

PubMed ID

10953551 (在PubMed

]

文摘

作品简介:分子遗传学的进展导致遗传性疾病的病理生理机制的发现以及更好的诊断和有效的治疗。一些有缺陷的ge - nes被发现在不同的染色体(3、4、7、11和21条染色体),以及他们之间的关系与某些类型的LQTS(长QT综合征)。基因功能障碍导致离子通道的功能障碍,而因此导致心肌复极化时间长的。这些变化表现在心电图QT间隔的持续时间延长(超过0.44秒)。家庭形式的LQTS作为常染色体显性遗传的(罗马病房综合症)和常染色体隐性(Jervell Lange-Neilsen综合征)。的最终形式定义LQTS即使有听力损失。临床调查:恶性室性心律失常、晕厥和猝死。电压门控离子通道的分子结构:时间可以由钠和钾电压门控离子通道。心脏动作电位高原是一个指标的出入口离子电流的平衡。在这个过程中几种潜在的两个电流被激活:向内去极化的电流(它发生在Na渠道)和向外再极化电流(这发生在K通道)。 Na channels are polypeptides incorporated in cell membrane. Their main function is to control excitability in myocardial cell. They consist of two subunits: alpha and beta. Class Ib of anty-arrhythmics (Lidocaine, Mexiletine and Tocainide) as well as Diphenylhydantoin blocks Na channels in the state of inactivation, in fact, during the depolarization of the cell. For controlling the cardiac voltage-gated potential the most important are voltage-sensitive K channels. For appearance of K ions delayed refraction of K channels (Kv) is of importance. Depending on the velocity of activation, Kv are divided into two groups: channels with rapid activation (Kvr) and channels with slow activation (Kvs). By activation of these delayed rectification channels (Kv) beta agonists shorten the action potential of the heart. GENETIC ASPECTS OF LQTS: Five loci which are connected with Romano Ward's familial form of LQTS have been described up to now. Specific mutant gene is responsible for function of K channels and it is located on short branch (part) of the 11-th pair of chromosome 11p15.5 (KVLQT-LQT1), long branch of the 7-th pair of chromosomes 7q35-36 (K- HERG-LQT2), as well as on the 21-st pair of chromosome (KCNE1-LQT5). Defective gene which is responsible for the function of Na channels is located on the short branch of chromosome 3p21-24 (SCN5A-LQT3). The gene which is located on the long branch of the 4-th pair of chromosome 4q25-27 (LQT4) has not been examined sufficiently. Persons with Jevell Lange-Neilsen syndrome inherit pathological allele from both parents (KvLQT1 or LQT5-minK). CONNECTION BETWEEN ION CHANNELS AND GENE MUTATION: Among all genes which are responsible for LQTS the most examined one is the so-called HERG gene located on the 7-th pair of chromosome (LQT2). Mutation of this gene leads to reduction in strength of outward K currents or to the dysfunction of K channel proteins. Mutant gene causes so-called missense mutation, in fact wrong change of amino acid in the protein chain. Among all described LQTS the most frequent and the most malignant form is LQT1. In 99% cases psychophysical stress can cause arrhythmia, syncope or sudden death. LQT3 and LQT5 are very rare. CONCLUSION: Genetic screening in LQTS patients provides discovery of risk population which demands anti-arrhythmic therapy with beta-blockers. A lot of arguments speak in favour of genetic screening in cases with LQTS. It is considered that if the diagnosis is known, genetic testing is not necessary, but it is useful. Moreover, it is obligatory in symptomatic cases as well as in those with suspected diagnosis of LQTS.

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药物靶点

药物	目标	类	生物	药理作用	行动
妥卡尼	钠离子通道蛋白类型5α亚基	蛋白质	人类	是的	抑制剂	细节