Arrhythmia genetics: Not dark and lite, but 50 shades of gray.
Arrhythmia genetics: Not dark and lite, but 50 shades of gray.
复制标题
心律失常遗传学：不是黑暗和淡雅，而是50度灰色。
DOI：
10.1016/j.hrthm.2018.04.031
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发表时间：
2018
期刊：
影响因子：
5.5
通讯作者：
Kroncke,Brett
中科院分区：
文献类型：
--
作者：
Roden,DanM;Glazer,AndrewM;Kroncke,Brett
先天性长QT综合征（cLQTS）在半个多世纪前首次被描述：我们现在认识到多种遗传和临床亚型，对该疾病的探索不仅为家庭筛查提供了信息，而且为我们对复极电生理学的基本理解提供了信息。伴随这些新知识而来的是一系列新的挑战，这些挑战集中在解释已知cLQTS疾病基因中变体的存在与其与表型的关系。有超过12种致病基因（其中一些并没有非常有力的证据表明与疾病有关）和数百种突变与疾病有合理的关系。面对突变，遗传学家有一套工具来驱动致病性评估：该变异在体外测试中产生异常功能，在一个亲属中与表型分离，在全球多个受影响个体中发现，并且在祖先中罕见。1
The congenital long QT syndromes (cLQTS) were first described over half a century ago: we now recognize multiple genetic and clinical subtypes and the exploration of the disease has informed not only family screening but also our fundamental understanding of the electrophysiology of repolarization. Along with this new knowledge has come a new set of challenges centered around interpretation of the relationship between the presence of a variant in a known cLQTS disease gene and its relationship to phenotype.There are over a dozen disease genes (some with not terribly robust evidence of association with disease) and hundreds of mutations that have a reasonable relationship to the disease. Faced with a mutation, the geneticist has a set of tools that drive assessment of pathogenicity: the variant generates abnormal function in in vitro testing, segregates with phenotype across a kindred, has been seen in multiple affected individuals across the globe, and is rare across ancestries. 1