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

Int J Legal Med. 2016 Mar;130(2):317-22. doi: 10.1007/s00414-015-1275-2. Epub 2015 Nov 19.

Abstract

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.

Keywords: Brugada syndrome; Cardiac arrhythmia; DSP gene; Sudden unexplained nocturnal death syndrome; Variant.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brugada Syndrome / genetics*
  • China
  • Death, Sudden / etiology*
  • Desmoplakins / genetics*
  • Ethnic Groups / genetics*
  • Forensic Genetics
  • Genetic Variation*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Young Adult

Substances

  • Desmoplakins