复合突变:严重长qt综合症的常见原因。
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Westenskow P, Splawski我,盖千瓦,基廷MT, Sanguinetti MC
复合突变:严重长qt综合症的常见原因。
循环。2004年4月20日,109 (15):1834 - 41。Epub 2004年3月29日。
- PubMed ID
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15051636 (在PubMed]
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背景:长QT综合征(LQTS)可能会影响个人从心律失常猝死。尽管大多数LQTS个人没有心脏事件,显著的表型变异存在于家庭。渊源者可以非常症状。这种表型变异的机制还不了解。方法和结果:基因分析KVLQT1, HERG, KCNE1, KCNE2, SCN5A发现复合突变252年20 LQTS渊源者(7.9%)。2突变携带者间隔较长高职院校学前教育专业(527 + / -54和489 + / -44 ms;P < 0.001);所有经历过心脏事件(20 20(100%)和128年的178 (72%);P < 0.01)和3.5倍更有可能有心脏骤停(16 9(56%)和167年45 (27%);P < 0.01; OR, 3.5; 95% CI, 1.2 to 9.9) compared with probands with 1 or no identified mutation. Two-microelectrode voltage clamp of Xenopus oocytes was used to characterize the properties of variant slow delayed rectifier potassium (I(Ks)) channels identified in 7 of the probands. When wild-type and variant subunits were coexpressed in appropriate ratios to mimic the genotype of the proband, the reduction in I(Ks) density was equivalent to the additive effects of the single mutations. CONCLUSIONS: LQTS-associated compound mutations cause a severe phenotype and are more common than expected. Individuals with compound mutations need to be identified, and their management should be tailored to their increased risk for arrhythmias.