Genetic diagnosis of acute aortic dissection in South China Han population using next-generation sequencing

Int J Legal Med. 2018 Sep;132(5):1273-1280. doi: 10.1007/s00414-018-1890-9. Epub 2018 Jul 28.


Acute aortic dissection (AAD) is a clinically "silent," but emergent and life-threatening cardiovascular disease, and hereditary factors play an important etiologic role in the development of AAD. The purposes of this study are to definitize the diagnostic yield of 59 AAD patients, investigate the molecular pathological spectrum of AAD by NGS, and explore the future preclinical prospects of genetic diagnosis on AAD high-risk groups. We performed next-generation sequencing (NGS) based on screening of the 69 currently aortic dissections/aneurysms-associated genes on 59 sporadic AAD samples from South China. A Kaplan-Meier survival curve was constructed to compare the event-free survival depending on variant number. Overall, 67 variants were detected in 39 patients, among which 4 patients were identified with pathogenic variants and 13 patients were diagnosed with likely pathogenic variants. Seventeen genotype positive patients were identified in aggregate, and the diagnostic yield of our study is 28.8%. All genotype-positive variants were distributed in 11 genes, FBN1 variants were in the largest number among genotype-positive variants, which were detected for 4 times, ACTA2 for 3 times, ABCC6 and TGFBR1 twice, and NOS3, MYLK, XYLT1, TIMP4, TGFBR2, CNTN3, and PON1 once. Individuals with three or more variants showed shorter mean event-free survival than patients with fewer variants. Our observations broaden the genetic pathological spectrum of AAD. Furthermore, our research uncovered two susceptibility genes FBN1 and ACTA2 for Stanford type A AAD patients. Finally, our study concluded that the number of variants an individual harbored was an important consideration in risk stratification for individualized prediction and disease diagnosis.

Keywords: Acute aortic dissection; Diagnostic yield; Genetic diagnosis; Next-generation sequencing.

MeSH terms

  • Aneurysm, Dissecting / diagnosis*
  • Aneurysm, Dissecting / genetics*
  • Aneurysm, Dissecting / mortality
  • Aortic Aneurysm, Thoracic / diagnosis*
  • Aortic Aneurysm, Thoracic / genetics*
  • Aortic Aneurysm, Thoracic / mortality
  • Aryldialkylphosphatase
  • China
  • Disease-Free Survival
  • Female
  • Genetic Association Studies
  • Genetic Testing
  • Genotype
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mutation / genetics


  • Aryldialkylphosphatase
  • PON1 protein, human