1970-2020: 50 years of research on the long QT syndrome-from almost zero knowledge to precision medicine
1970-2020: 50 years of research on the long QT syndrome-from almost zero knowledge to precision medicine
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DOI：
10.1093/eurheartj/ehaa769
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发表时间：
2021-03-14
影响因子：
39.3
通讯作者：
Schwartz, Peter J.
中科院分区：
文献类型：
--
作者：
Schwartz, Peter J.
对于我们这些从事临床研究的人来说，很少有机会开始研究一种相当模糊的疾病，仍然在很大程度上未被探索，并随着它的成熟而成为临床医生和基础科学家都感兴趣的医学实体，而且这样做了整整50年。这就是我在不懈地追求被称为长QT综合征（LQTS）的有趣疾病中的特权。这篇文章从我遇到的第一个受LOTS影响的病人开始，当时只有少数心脏病专家看到了类似的病例，并继续进行了一系列的努力，有些听起来有些业余，最终与许多出色的合作伙伴和同事一起描述和理解了疾病的自然史和最有效的治疗方法。然后，它涉及到我们的LQTS国际登记处，其有据可查的家谱，构成了20世纪90年代重大遗传发现的必要跳板。由于遗传数据的爆炸，我自己的兴趣首先集中在有趣的基因型-表型相关性上，然后是“修饰基因”，试图理解为什么具有相同致病突变的家庭成员可能有相反的临床病史。从那时起，研究人员开始研究iPS衍生的心肌细胞，用于解开修饰基因的特定作用机制并探索新的治疗策略。这段漫长而有价值的旅程会继续下去，因为未知的魅力和吸引力是不可抗拒的。
To those of us involved in clinical research it seldom happens to begin working on a rather obscure disease, still largely unexplored, and to follow its ripening into a medical entity of large interest to clinicians and basic scientists alike, and moreover to do so for exactly 50 years. This is what has been my privilege in the relentless pursuit of the intriguing disease known as the long QT syndrome (LQTS). This essay begins with the encounter with my first patient affected by LOTS when just a handful of cardiologists had seen similar cases and continues with the series of efforts, some sound some amateurish, which eventually led-together with many brilliant partners and associates-to describe and understand the natural history of the disease and the most effective therapies. It then touches on how our International Registry for LQTS, with its well-documented family trees, constituted the necessary springboard for the major genetic discoveries of the 1990s. From the explosion of genetic data, my own interest focused first on the intriguing genotype-phenotype correlation and then on 'modifier genes', in the attempt of understanding why family members with the same disease-causing mutation could have an opposite clinical history. And from there on to iPS-derived cardiomyocytes, used to unravelling the specific mechanisms of action of modifier genes and to exploring novel therapeutic strategies. This long, and highly rewarding, journey continues because the fascination and the attraction of the unknown are irresistible.