A novel three base-pair deletion in domain two of the cardiac sodium channel causes Brugada syndrome

作者：Tan, Boon Yew; Wang, Luokai; Uttamchandani, Mahesh; Barajas-Martinez, Hector; Dumaine, Robert; Morin, Nathalie; Ching, Chi Keong; Ho, Kah Leng; Chong, Daniel Thuan Tee; Chow, Weien; Yap, Eric Peng Huat; Moochhala, Shabbir; Hu, Dan^*; Yong, Rita Yu Yin^*; Teo, Wee Siong^*

来源：Journal of Electrocardiology, 2018, 51(4): 667-673.

DOI：10.1016/j.jelectrocard.2018.03.009

• Brugada syndrome
• Channelopathy
• Genetic testing
• Nav1.5
• SCN5A

Introduction: Mutations within SCN5A are found in a significant proportion (15-30%) of Brugada syndrome (BrS) cases and impair sodium transport across excitable cardiac cells that mediate ventricular contractions. Genetic testing offers a means to clinically assess and manage affected individuals and their family members.
Methods and results: The proband at age 44 years old exhibited a syncopal event during exercise, and presented later with a spontaneous type-I BrS pattern on 12 lead resting electrocardiogram (ECG). Mutational analysis performed across all SCN5A exons revealed a unique three base-pair deletion p.M741_T742delinsl (c.2223_2225delGAC), in a heterozygous state in the proband and 2 siblings. This mutation was not seen in a cohort of 105 ethnicity-matched controls or in public genome databases. Patch clamp electrophysiology study conducted in TSA201 cells showed an abolishment of sodium current (INa). The proband, and several relatives, also harboured a known SCN5A variant, p.R1193Q (c.3578G>A).
Conclusion: Our study has demonstrated the deleterious effect of a novel SCN5A mutation p.M741_T742delinsl (c.2223_2225delGAC). The findings highlight the complex effects of gender and age in phenotype manifestation. It also offers insights into improving the long-term management of BrS, and the utility of cascade genetic screening for risk stratification.

• 出版日期2018-8
• 单位南阳理工学院; 武汉大学