Identification of Novel SCN5A Single Nucleotide Variants in Brugada Syndrome: A Territory-Wide Study From Hong Kong

Gary Tse; Sharen Lee; Tong Liu; Ho Chuen Yuen; Ian Chi Kei Wong; Chloe Mak; Ngai Shing Mok; Wing Tak Wong

doi:10.3389/fphys.2020.574590

Identification of Novel SCN5A Single Nucleotide Variants in Brugada Syndrome: A Territory-Wide Study From Hong Kong

Front Physiol. 2020 Sep 18:11:574590. doi: 10.3389/fphys.2020.574590. eCollection 2020.

Authors

Gary Tse^{1

2}, Sharen Lee³, Tong Liu², Ho Chuen Yuen⁴, Ian Chi Kei Wong^{5

6}, Chloe Mak⁷, Ngai Shing Mok⁴, Wing Tak Wong⁸

Affiliations

¹ Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, China.
² Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China.
³ Laboratory of Cardiovascular Physiology, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China.
⁴ Department of Medicine and Geriatrics, Princess Margaret Hospital, Kowloon, China.
⁵ Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, China.
⁶ School of Pharmacy, University College London, London, United Kingdom.
⁷ Department of Pathology, Hong Kong Children's Hospital, Kowloon, China.
⁸ State Key Laboratory of Agrobiotechnology (CUHK), School of Life Sciences, The Chinese University of Hong Kong, Shatin, China.

Abstract

Background: The aim of this study is to report on the genetic composition of Brugada syndrome (BrS) patients undergoing genetic testing in Hong Kong.

Methods: Patients with suspected BrS who presented to the Hospital Authority of Hong Kong between 1997 and 2019, and underwent genetic testing, were analyzed retrospectively.

Results: A total of 65 subjects were included (n = 65, 88% male, median presenting age 42 [30-54] years old, 58% type 1 pattern). Twenty-two subjects (34%) showed abnormal genetic test results, identifying the following six novel, pathogenic or likely pathogenic mutations in SCN5A: c.674G > A, c.2024-11T > A, c.2042A > C, c.4279G > T, c.5689C > T, c.429del. Twenty subjects (31%) in the cohort suffered from spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF) and 18 (28%) had incident VT/VF over a median follow-up of 83 [Q1-Q3: 52-112] months. Univariate Cox regression demonstrated that syncope (hazard ratio [HR]: 4.27 [0.95-19.30]; P = 0.059), prior VT/VF (HR: 21.34 [5.74-79.31; P < 0.0001) and T-wave axis (HR: 0.970 [0.944-0.998]; P = 0.036) achieved P < 0.10 for predicting incident VT/VF. After multivariate adjustment, only prior VT/VF remained a significant predictor (HR: 12.39 [2.97-51.67], P = 0.001).

Conclusion: This study identified novel mutations in SCN5A in a Chinese cohort of BrS patients.

Keywords: Brugada syndrome; SCN5A; Sudden cardiac death; risk stratification; ventricular arrhythmias.