Skip to main content
Erschienen in: International Journal of Legal Medicine 5/2018

28.07.2018 | Original Article

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

verfasst von: Jinxiang Zheng, Jian Guo, Lei Huang, Qiuping Wu, Kun Yin, Lin Wang, Tongda Zhang, Li Quan, Qianhao Zhao, Jianding Cheng

Erschienen in: International Journal of Legal Medicine | Ausgabe 5/2018

Einloggen, um Zugang zu erhalten

Abstract

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Clouse WD, Hallett JW Jr, Schaff HV et al (2004) Acute aortic dissection: population-based incidence compared with degenerative aortic aneurysm rupture. Mayo Clin Proc 79(2):176–180CrossRefPubMed Clouse WD, Hallett JW Jr, Schaff HV et al (2004) Acute aortic dissection: population-based incidence compared with degenerative aortic aneurysm rupture. Mayo Clin Proc 79(2):176–180CrossRefPubMed
2.
Zurück zum Zitat Meszaros I, Morocz J, Szlavi J et al (2000) Epidemiology and clinicopathology of aortic dissection. Chest 117(5):1271–1278CrossRefPubMed Meszaros I, Morocz J, Szlavi J et al (2000) Epidemiology and clinicopathology of aortic dissection. Chest 117(5):1271–1278CrossRefPubMed
8.
Zurück zum Zitat Katoh H, Suzuki T, Hiroi Y et al (1995) Diagnosis of aortic dissection by immunoassay for circulating smooth muscle myosin. Lancet 345(8943):191–192CrossRefPubMed Katoh H, Suzuki T, Hiroi Y et al (1995) Diagnosis of aortic dissection by immunoassay for circulating smooth muscle myosin. Lancet 345(8943):191–192CrossRefPubMed
9.
Zurück zum Zitat Katoh H, Suzuki T, Yokomori K et al (1995) A novel immunoassay of smooth muscle myosin heavy chain in serum. J Immunol Methods 185(1):57–63CrossRefPubMed Katoh H, Suzuki T, Yokomori K et al (1995) A novel immunoassay of smooth muscle myosin heavy chain in serum. J Immunol Methods 185(1):57–63CrossRefPubMed
10.
Zurück zum Zitat Suzuki T, Katoh H, Watanabe M et al (1996) Novel biochemical diagnostic method for aortic dissection. Results of a prospective study using an immunoassay of smooth muscle myosin heavy chain. Circulation 93(6):1244–1249CrossRefPubMed Suzuki T, Katoh H, Watanabe M et al (1996) Novel biochemical diagnostic method for aortic dissection. Results of a prospective study using an immunoassay of smooth muscle myosin heavy chain. Circulation 93(6):1244–1249CrossRefPubMed
11.
Zurück zum Zitat Suzuki T, Katoh H, Tsuchio Y et al (2000) Diagnostic implications of elevated levels of smooth-muscle myosin heavy-chain protein in acute aortic dissection. The smooth muscle myosin heavy chain study. Ann Intern Med 133(7):537–541CrossRefPubMed Suzuki T, Katoh H, Tsuchio Y et al (2000) Diagnostic implications of elevated levels of smooth-muscle myosin heavy-chain protein in acute aortic dissection. The smooth muscle myosin heavy chain study. Ann Intern Med 133(7):537–541CrossRefPubMed
13.
Zurück zum Zitat Suzuki T, Katoh H, Nagai R (1999) Biochemical diagnosis of aortic dissection: from bench to bedside. Jpn Heart J 40(5):527–534CrossRefPubMed Suzuki T, Katoh H, Nagai R (1999) Biochemical diagnosis of aortic dissection: from bench to bedside. Jpn Heart J 40(5):527–534CrossRefPubMed
32.
Zurück zum Zitat Zhao XL, Chen J, Cui YL, Wu F, Hu DY (2006) Current status of primary hypertension in China: an epidemiological study of 12 provinces, 1 autonomous regions, and 1 municipality. Zhonghua Yi Xue Za Zhi 86(16):1148–1152PubMed Zhao XL, Chen J, Cui YL, Wu F, Hu DY (2006) Current status of primary hypertension in China: an epidemiological study of 12 provinces, 1 autonomous regions, and 1 municipality. Zhonghua Yi Xue Za Zhi 86(16):1148–1152PubMed
33.
Zurück zum Zitat Centers for Disease C, Prevention (2013) Racial/ethnic disparities in the awareness, treatment, and control of hypertension - United States, 2003-2010. MMWR Morb Mortal Wkly Rep 62(18):351–355 Centers for Disease C, Prevention (2013) Racial/ethnic disparities in the awareness, treatment, and control of hypertension - United States, 2003-2010. MMWR Morb Mortal Wkly Rep 62(18):351–355
34.
Zurück zum Zitat Hagan PG, Nienaber CA, Isselbacher EM et al (2000) The international registry of acute aortic dissection (IRAD): new insights into an old disease. JAMA 283(7):897–903CrossRefPubMed Hagan PG, Nienaber CA, Isselbacher EM et al (2000) The international registry of acute aortic dissection (IRAD): new insights into an old disease. JAMA 283(7):897–903CrossRefPubMed
37.
Zurück zum Zitat Plomp AS, Florijn RJ, Ten Brink J et al (2008) ABCC6 mutations in pseudoxanthoma elasticum: an update including eight novel ones. Mol Vis 14:118–124PubMedPubMedCentral Plomp AS, Florijn RJ, Ten Brink J et al (2008) ABCC6 mutations in pseudoxanthoma elasticum: an update including eight novel ones. Mol Vis 14:118–124PubMedPubMedCentral
Metadaten
Titel
Genetic diagnosis of acute aortic dissection in South China Han population using next-generation sequencing
verfasst von
Jinxiang Zheng
Jian Guo
Lei Huang
Qiuping Wu
Kun Yin
Lin Wang
Tongda Zhang
Li Quan
Qianhao Zhao
Jianding Cheng
Publikationsdatum
28.07.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
International Journal of Legal Medicine / Ausgabe 5/2018
Print ISSN: 0937-9827
Elektronische ISSN: 1437-1596
DOI
https://doi.org/10.1007/s00414-018-1890-9

Weitere Artikel der Ausgabe 5/2018

International Journal of Legal Medicine 5/2018 Zur Ausgabe

Neu im Fachgebiet Rechtsmedizin