Identification of rare variants of DSP gene in sudden unexplained nocturnal death syndrome in the southern Chinese Han population

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• 作者：Qianhao Zhao ; Yili Chen ; Longlun Peng ; Rui Gao…
• 关键词：Sudden unexplained nocturnal death syndrome ; Brugada syndrome ; DSP gene ; Cardiac arrhythmia ; Variant
• 刊名：International Journal of Legal Medicine
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：130
• 期：2
• 页码：317-322
• 全文大小：362 KB
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• 作者单位：Qianhao Zhao (1)
  Yili Chen (2)
  Longlun Peng (2)
  Rui Gao (3)
  Nian Liu (4)
  Pingping Jiang (3)
  Chao Liu (3)
  Shuangbo Tang (1)
  Li Quan (1)
  Jonathan C. Makielski (5)
  Jianding Cheng (1)
  
  1. Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74, Zhongshan 2nd Road, Guangzhou, Guangdong, 510080, China
  2. Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China
  3. BGI-Shenzhen, Shenzhen, 518083, China
  4. Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
  5. Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison, WI, 53792, USA
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Forensic Medicine
  Medical Law
  Medicine/Public Health, general
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1437-1596

文摘

Sudden unexplained nocturnal death syndrome (SUNDS) is a perplexing disorder to both forensic pathologists and clinic physicians. Desmoplakin (DSP) gene was the first desmosomal gene linked to arrhythmogenic right ventricular cardiomyopathy (ARVC) which was associated with sudden death. To identify the genetic variants of the DSP gene in SUNDS in the southern Chinese Han population, we genetically screened the DSP gene in 40 sporadic SUNDS victims, 16 Brugada syndrome (BrS) patients, and 2 early repolarization syndrome (ERS) patients using next generation sequencing (NSG) and direct Sanger sequencing. A total of 10 genetic variants of the DSP gene were detected in 11 cases, comprised of two novel missense mutations (p.I125F and p.D521A) and eight previously reported rare variants. Of eight reported variants, two were previously considered pathogenic (p.Q90R and p.R2639Q), three were predicted in silico to be pathogenic (p.R315C, p.E1357D and p.D2579H), and the rest three were predicted to be benign (p.N1234S, p.R1308Q, and p.T2267S). This is the first report of DSP genetic screening in Chinese SUNDS and Brugada syndrome. Our results imply that DSP mutations contribute to the genetic cause of some SUNDS victims and maybe a new susceptible gene for Brugada syndrome.