International Journal of Legal Medicine

, Volume 132, Issue 5, pp 1273–1280 | Cite as

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

  • Jinxiang Zheng
  • Jian Guo
  • Lei Huang
  • Qiuping Wu
  • Kun Yin
  • Lin Wang
  • Tongda Zhang
  • Li Quan
  • Qianhao ZhaoEmail author
  • Jianding ChengEmail author
Original Article


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.


Acute aortic dissection Next-generation sequencing Genetic diagnosis Diagnostic yield 

Abbreviations and acronyms


Acute aortic dissection


Next-generation sequencing


Aortic dissection


Sudden cardiac death


Computed tomography angiography


Transforming growth factor-beta


Marfan syndrome


Thoracic aortic aneurysms and dissections


Extracellular matrix


Variant with uncertain significance


Registry of Aortic Dissection in China


International Registry of Acute Aortic Dissection



This work was supported by National Key R&D Program (2017YFC0803502) of China, the Key Program (81430046) from the National Natural Science Foundation of China, and the grant (17ykzd03) from Sun Yat-sen University.

Compliance with ethical standards

All data and sample collection were in strict accordance with ethics guidelines of Zhongshan School of Medicine, Sun Yat-sen University.

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from the healthy controls, patients, or legal representatives of the victims. The principles outlined in the Declaration of Helsinki were followed. The research was approved for human research by the Ethics Committee of Sun Yat-sen University.

Supplementary material

414_2018_1890_MOESM1_ESM.docx (30 kb)
ESM 1 (DOCX 29 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Faculty of Forensic Medicine, Zhongshan School of MedicineSun Yat-Sen University, GuangzhouGuangzhouChina
  2. 2.Guangdong Province Translational Forensic Medicine Engineering Technology Research CenterSun Yat-Sen UniversityGuangzhouChina
  3. 3.Department of Forensic Medicine, School of Basic Medical SciencesZhengzhou UniversityZhengzhouChina
  4. 4.BGI-ShenzhenShenzhenChina
  5. 5.China National GeneBank, BGI-ShenzhenShenzhenChina

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