Author + information
- Yubi Lin1,2,
- Zili Liao1,
- Siqi He2,1,
- Ruilin Liu3,
- Yongzheng Peng4,
- Nan Yu4,
- Hang Qi4,
- Jia Chen5,
- Ruiling Feng2,1,
- Zifeng Huang2,1,
- Heping Lei1,
- Yang Liu1,
- Fang Rao1,
- Chunyu Deng1,
- Yumei Xue1,
- Kejian Wang6,
- Bin Zhang1,
- Hua Yao1∗ and
- Shulin Wu1
- 1Guangdong General Hospital and The First Clinical College Affiliated to Medical School, South China University of Technology; Guangdong Cardiovascular Institute; Guangdong Provincial Key Laboratory of South China structural Heart Disease;, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China
- 2The First Affiliated Hospital of Jinan University, Guangzhou, China
- 3Shunde Hospital of Southern Medical University, Shunde, China
- 4Department of Clinical Laboratory, Zhujiang Hospital of Southern Medical University, Guangzhou, China
- 5Second Department of Cardiology, Guangdong No.2 Provincial People’s Hospital, Guangzhou, P.R. China
- 6Lin He’s Academician Workstation of New Medicine and Clinical Translation at The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, P.R. China
This study aimed to identify the pathogenic mutation in a Chinese family with unexplained sudden death (USD) or occasional syncope.
Whole exome sequencing and gene chip sequencing were respectively conducted for two related patients. The genetic data was screened using the 1000 genomes project and SNP database (PubMed), and the identified mutations were assessed for predicted pathogenicity using the SIFT and Polyphen-2 algorithms.
We identified a heterozygous mutation in the RYR2 gene at c.490C>T (p.P164S), highly conserved across all species, in three members of this family, while another heterozygous de novo mutation in SCN5A at c.5576G>A p.R1859H was detected in one family member. Both variants were verified by Sanger sequencing. Importantly, RYR2 p.P164S is associated with the risk of sudden cardiac death, such as in catecholaminergic polymorphic ventricular tachycardia.
A pathogenic mutation in RYR2 (p.P164S) is the likely cause of USD in a Chinese family associated with malignant ventricular arrhythmias. Whole exome and chip gene sequencing can be useful for discovering the genetic causes of USD.