Introduction

Skeletal muscle channelopathies are rare inherited conditions that cause significant morbidity and impact on quality of life. Some subsets have a mortality risk. Improved genetic methodology and understanding of phenotypes have improved diagnostic accuracy and yield.

Areas covered

We discuss diagnostic advances since the advent of next-generation sequencing and the role of whole exome and genome sequencing. Advances in genotype-phenotype-functional correlations have improved understanding of inheritance and phenotypes. We outline new phenotypes, particularly in the pediatric setting and consider co-existing mutations that may act as genetic modifiers. We also discuss four newly identified genes associated with skeletal muscle channelopathies.

Expert opinion

Next-generation sequencing using gene panels has improved diagnostic rates, identified new mutations, and discovered patients with co-existing pathogenic mutations (‘double trouble’). This field has previously focussed on single genes, but we are now beginning to understand interactions between co-existing mutations, genetic modifiers, and their role in pathomechanisms. New genetic observations in pediatric presentations of channelopathies broadens our understanding of the conditions. Genetic and mechanistic advances have increased the potential to develop treatments.

中文翻译：

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改进骨骼肌通道病的遗传诊断。

介绍

骨骼肌通道病是一种罕见的遗传性疾病，会导致严重的发病率并影响生活质量。一些子集有死亡风险。改进的遗传方法和对表型的理解提高了诊断准确性和产量。

涵盖的领域

我们讨论了自下一代测序出现以来的诊断进展以及全外显子组和基因组测序的作用。基因型-表型-功能相关性的进展提高了对遗传和表型的理解。我们概述了新的表型，特别是在儿科环境中，并考虑了可能作为遗传修饰剂的共存突变。我们还讨论了四个新发现的与骨骼肌通道病相关的基因。

专家意见

使用基因组的下一代测序提高了诊断率，发现了新的突变，并发现了同时存在致病突变的患者（“双重麻烦”）。该领域以前主要关注单个基因，但我们现在开始了解共存突变、遗传修饰因子之间的相互作用，以及它们在病理机制中的作用。通道病儿科表现的新遗传观察拓宽了我们对这些病症的理解。遗传和机制的进步增加了开发治疗方法的潜力。