Gualandi Francesca, Zaraket Fatima, Malagù Michele, Parmeggiani Giulia, Trabanelli Cecilia, Fini Sergio, Dang Xiao, Wei Xiaoming, Fang Mingyan, Bertini Matteo, Ferrari Roberto, Ferlini Alessandra
Medical Genetics Logistic Unit (UOL), Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Cardiology. 2017;137(4):256-260. doi: 10.1159/000471792. Epub 2017 May 12.
Brugada syndrome is a primary arrhythmic syndrome that accounts for 20% of all sudden cardiac death cases in individuals with a structurally normal heart. Pathogenic variants associated with Brugada syndrome have been identified in over 19 genes, with SCN5A as a pivotal gene accounting for nearly 30% of cases. In contrast to other arrhythmogenic channelopathies (such as long QT syndrome), digenic inheritance has never been reported in Brugada syndrome. Exploring 66 cardiac genes using a new custom next-generation sequencing panel, we identified a double heterozygosity for pathogenic mutations in SCN5A and TRPM4 in a Brugada syndrome patient. The parents were heterozygous for each variation. This novel finding highlights the role of mutation load in Brugada syndrome and strongly suggests the adoption of a gene panel to obtain an accurate genetic diagnosis, which is mandatory for risk stratification, prevention, and therapy.
布加综合征是一种原发性心律失常综合征，在心脏结构正常的个体中占所有心源性猝死病例的20%。已在超过19个基因中鉴定出与布加综合征相关的致病变异，其中SCN5A是关键基因，占近30%的病例。与其他致心律失常性离子通道病（如长QT综合征）不同，布加综合征从未报道过双基因遗传。我们使用新的定制下一代测序面板对66个心脏基因进行检测，在一名布加综合征患者中发现了SCN5A和TRPM4致病突变的双重杂合性。父母双方对每个变异均为杂合子。这一新发现突出了突变负荷在布加综合征中的作用，并强烈建议采用基因检测面板以获得准确的基因诊断，这对于风险分层、预防和治疗至关重要。
