Priori S G
Molecular Cardiology Laboratories, Fondazione Salvatore Mangeri, Pavia, Italy.
Rev Port Cardiol. 1998 Nov;17 Suppl 3:III27-38.
Molecular genetics is progressively entering clinical practice. This new approach is modifying medical thinking as it becomes possible to diagnose diseases in their presymptomatic phase. It is therefore important for physicians to become acquainted with the "language" and the "methodology" of molecular biologists in order to balance opposite attitudes of the novice, i.e. skepticism and over-expectation, and to establish a fruitful interaction with the molecular diagnostic laboratories. Long QT syndrome is an inherited disease that few years ago was still called "idiopathic" as the underlying causes were unknown. Clinicians are now becoming aware that what was considered as one disease is actually the common phenotype of defects in at least five different LQT-related genes and that therefore clinical heterogeneity is likely to parallel genetic heterogeneity. The first steps have been undertaken to define the relative prevalence of the molecular variants of LQTS, to develop gene-specific therapy and to perform risk stratification based on the molecular defect. In this article, current knowledge of the molecular bases of LQTS is reviewed and criteria are proposed to help defining 1) when it is appropriate to attempt molecular diagnosis, 2) how to interpret results of the diagnostic laboratory and 3) how molecular diagnosis may affect patients management.
分子遗传学正逐渐进入临床实践。这种新方法正在改变医学思维，因为现在有可能在疾病的症状前期进行诊断。因此，医生熟悉分子生物学家的“语言”和“方法学”很重要，以便平衡新手的两种相反态度，即怀疑和过度期望，并与分子诊断实验室建立富有成效的互动。长QT综合征是一种遗传性疾病，就在几年前，由于其潜在病因不明，它仍被称为“特发性”。临床医生现在逐渐意识到，过去被认为是一种疾病的情况实际上是至少五种不同的长QT相关基因缺陷的共同表型，因此临床异质性可能与基因异质性平行。已经采取了初步措施来确定长QT综合征分子变异的相对患病率，开发基因特异性疗法，并根据分子缺陷进行风险分层。在本文中，我们回顾了长QT综合征分子基础的当前知识，并提出了一些标准，以帮助确定：1）何时适合尝试分子诊断；2）如何解释诊断实验室的结果；3）分子诊断如何影响患者的管理。
