Improving genetic diagnostics of skeletal muscle channelopathies.

Improving genetic diagnostics of skeletal muscle channelopathies. Expert Rev Mol Diagn. 2020 Jul 12;:1-12 Authors: Vivekanandam V, Männikkö R, Matthews E, Hanna MG Abstract 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 cond...
Source: Expert Review of Molecular Diagnostics - Category: Laboratory Medicine Tags: Expert Rev Mol Diagn Source Type: research