Skip to main content
Log in

Human aortic aneurysm genomic dictionary: is it possible?

  • Review Article
  • Published:
Indian Journal of Thoracic and Cardiovascular Surgery Aims and scope Submit manuscript

Abstract

Thoracic aortic aneurysm (TAA), a typically silent but frequently lethal disease, is strongly influenced by underlying genetics. Approximately 30 genes have been associated with syndromic and non-syndromic familial thoracic aortic aneurysm and dissection (TAAD) to date. An estimated 30% of patients with non-syndromic familial TAAD, which is typically inherited in an autosomal dominant manner, have a mutation in one of these genes. The underlying genetic mutation helps predict patients’ clinical presentation, risk of aortic dissection at small aortic sizes (< 5.0 cm), and risk of other cardiovascular disease. As a result, a TAAD genomic dictionary based on these genes is necessary to provide optimal patient care, but is not on its own sufficient as this disease is typically inherited with reduced penetrance and has widely variable expressivity. Next-generation sequencing has been and will continue to be critical for identifying novel genes and variants associated with TAAD as well as genotype-phenotype correlations that will allow for management to be targeted to not only the underlying gene harboring the pathogenic variant but also the specific mutation identified. The aortic dictionary, to which a clinician can turn to obtain information on clinical consequences of a specific genetic variants, is not only possible, but has been substantially written already. As additional entries to the dictionary are made, truly personalized, genetically based, aneurysm care can be delivered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Verstraeten A, Luyckx I, Loeys B. Aetiology and management of hereditary aortopathy. Nat Rev Cardiol. 2017;14:197–208.

    Article  CAS  PubMed  Google Scholar 

  2. Chau KH, Elefteriades JA. Natural history of thoracic aortic aneurysms: size matters, plus moving beyond size. Prog Cardiovasc Dis. 2013;56:74–80.

    Article  PubMed  Google Scholar 

  3. Pape LA, Tsai TT, Isselbacher EM, et al. Aortic diameter >or = 5.5 cm is not a good predictor of type A aortic dissection: observations from the International Registry of Acute Aortic Dissection (IRAD). Circulation. 2007;116:1120–7.

    Article  PubMed  Google Scholar 

  4. Howard DP, Banerjee A, Fairhead JF, Perkins J, Silver LE, Rothwell PM. Population-based study of incidence and outcome of acute aortic dissection and premorbid risk factor control: 10-year results from the Oxford Vascular Study. Circulation. 2013;127:2031–7.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Milewicz D, Hostetler E, Wallace S, Mellor-Crummey L, Gong L, Pannu H, et al. Precision medical and surgical management for thoracic aortic aneurysms and acute aortic dissections based on the causative mutant gene. J Cardiovasc Surg (Torino). 2016;57:172–7.

    Google Scholar 

  6. Pomianowski P, Elefteriades JA. The genetics and genomics of thoracic aortic disease. Ann Cardiothorac Surg. 2013;2:271–9.

    PubMed  PubMed Central  Google Scholar 

  7. Milewicz DM, Regalado ES, Shendure J, Nickerson DA, Guo DC. Successes and challenges of using whole exome sequencing to identify novel genes underlying an inherited predisposition for thoracic aortic aneurysms and acute aortic dissections. Trends Cardiovasc Med. 2014;24:53–60.

    Article  CAS  PubMed  Google Scholar 

  8. Albornoz G, Coady MA, Roberts M, et al. Familial thoracic aortic aneurysms and dissections - Incidence, modes of inheritance, and phenotypic patterns. Ann Thorac Surg. 2006;82:1400–6.

    Article  PubMed  Google Scholar 

  9. Milewicz DM, Chen H, Park ES, et al. Reduced penetrance and variable expressivity of familial thoracic aortic aneurysms/dissections. Am J Cardiol. 1998;82:474–9.

    Article  CAS  PubMed  Google Scholar 

  10. Bradley TJ, Bowdin SC, Morel CF, Pyeritz RE. The expanding clinical spectrum of extracardiovascular and cardiovascular manifestations of Heritable Thoracic Aortic Aneurysm and Dissection. Can J Cardiol. 2016;32:86–99.

    Article  PubMed  Google Scholar 

  11. Luyckx I, Loeys BL. The genetic architecture of non-syndromic thoracic aortic aneurysm. Heart. 2015;101:1678–84.

    Article  CAS  PubMed  Google Scholar 

  12. Biddinger A, Rocklin M, Coselli J, Milewicz DM. Familial thoracic aortic dilatations and dissections: a case control study. J Vasc Surg. 1997;25:506–11.

    Article  CAS  PubMed  Google Scholar 

  13. Coady MA, Davies RR, Roberts M, et al. Familial patterns of thoracic aortic aneurysms. Arch Surg. 1999;134:361–7.

    Article  CAS  PubMed  Google Scholar 

  14. Elefteriades JA, Farkas EA. Thoracic aortic aneurysm clinically pertinent controversies and uncertainties. J Am Coll Cardiol. 2010;55:841–57.

    Article  CAS  PubMed  Google Scholar 

  15. Chou AS, Ma WG, Mok SC, et al. Do Familial Aortic Dissections Tend to Occur at the Same Age? Ann Thorac Surg. 2017;103:546–50.

    Article  PubMed  Google Scholar 

  16. Sherrah AG, Andvik S, van der Linde D, et al. Nonsyndromic thoracic aortic aneurysm and dissection: outcomes with marfan syndrome versus bicuspid aortic valve aneurysm. J Am Coll Cardiol. 2016;67:618–26.

    Article  PubMed  Google Scholar 

  17. Milewicz DM, Regalado E. Heritable thoracic aortic disease overview. In: Adam MP, Ardinger HH, Pagon R, et al., editors. GeneReviews(R). Seattle (WA) 1993.

  18. Brownstein AJ, Ziganshin BA, Kuivaniemi H, Body SC, Bale AE, Elefteriades JA. Genes associated with thoracic aortic aneurysm and dissection: an update and clinical implications. Aorta (Stamford). 2017;5:11–20.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Andelfinger G, Loeys B, Dietz H. A decade of discovery in the genetic understanding of thoracic aortic disease. Can J Cardiol. 2016;32:13–25.

    Article  PubMed  Google Scholar 

  20. Disabella E, Grasso M, Gambarin FI, et al. Risk of dissection in thoracic aneurysms associated with mutations of smooth muscle alpha-actin 2 (ACTA2). Heart. 2011;97:321–6.

    Article  CAS  PubMed  Google Scholar 

  21. Guo DC, Pannu H, Tran-Fadulu V, et al. Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet. 2007;39:1488–93.

    Article  CAS  PubMed  Google Scholar 

  22. Meester JA, Vandeweyer G, Pintelon I, et al. Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections. Genet Med. 2017;19:386–95.

    Article  CAS  PubMed  Google Scholar 

  23. Schwarze U, Hata R, McKusick VA, et al. Rare autosomal recessive cardiac valvular form of Ehlers-Danlos syndrome results from mutations in the COL1A2 gene that activate the nonsense-mediated RNA decay pathway. Am J Hum Genet. 2004;74:917–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Germain DP. Ehlers-Danlos syndrome type IV. Orphanet J Rare Dis. 2007;2:32.

  25. Erbel R, Aboyans V, Boileau C, et al. ESC Guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2014;35:2873–926.

    Article  PubMed  Google Scholar 

  26. De Paepe A, Malfait F. The Ehlers-Danlos syndrome, a disorder with many faces. Clin Genet. 2012;82:1–11.

    Article  CAS  PubMed  Google Scholar 

  27. Monroe GR, Harakalova M, van der Crabben SN, et al. Familial Ehlers-Danlos syndrome with lethal arterial events caused by a mutation in COL5A1. Am J Med Genet A. 2015;167:1196–203.

    Article  CAS  PubMed  Google Scholar 

  28. Mehta S, Dhar SU, Birnbaum Y. Common iliac artery aneurysm and spontaneous dissection with contralateral iatrogenic common iliac artery dissection in classic ehlers-danlos syndrome. Int J Angiol. 2012;21:167–70.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Wenstrup RJ, Meyer RA, Lyle JS, et al. Prevalence of aortic root dilation in the Ehlers-Danlos syndrome. Genet Med. 2002;4:112–7.

    Article  PubMed  Google Scholar 

  30. Jelsig AM, Urban Z, Hucthagowder V, Nissen H, Ousager LB. Novel ELN mutation in a family with supravalvular aortic stenosis and intracranial aneurysm. Eur J Med Genet. 2017;60:110–3.

    Article  PubMed  Google Scholar 

  31. Callewaert B, Renard M, Hucthagowder V, et al. New insights into the pathogenesis of autosomal-dominant cutis laxa with report of five ELN mutations. Hum Mutat. 2011;32:445–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Szabo Z, Crepeau MW, Mitchell AL, et al. Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene. J Med Genet. 2006;43:255–8.

    Article  CAS  PubMed  Google Scholar 

  33. Capuano A, Bucciotti F, Farwell KD, et al. Diagnostic exome sequencing identifies a novel gene, EMILIN1, associated with autosomal-dominant hereditary connective tissue disease. Hum Mutat. 2016;37:84–97.

    Article  CAS  PubMed  Google Scholar 

  34. Morris SA, Orbach DB, Geva T, Singh MN, Gauvreau K, Lacro RV. Increased vertebral artery tortuosity index is associated with adverse outcomes in children and young adults with connective tissue disorders. Circulation. 2011;124:388–96.

    Article  PubMed  Google Scholar 

  35. Hiratzka LF, Bakris GL, Beckman JA, et al. ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the diagnosis and management of patients with thoracic aortic disease. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. J Am Coll Cardiol. 2010. 2010;55:e27–e129.

    Article  Google Scholar 

  36. Takeda N, Morita H, Fujita D, et al. Congenital contractural arachnodactyly complicated with aortic dilatation and dissection: Case report and review of literature. Am J Med Genet A. 2015;167A:2382–7.

    Article  CAS  PubMed  Google Scholar 

  37. Reinstein E, Frentz S, Morgan T, et al. Vascular and connective tissue anomalies associated with X-linked periventricular heterotopia due to mutations in Filamin A. Eur J Hum Genet. 2013;21:494–502.

    Article  CAS  PubMed  Google Scholar 

  38. Lange M, Kasper B, Bohring A, et al. 47 patients with FLNA associated periventricular nodular heterotopia. Orphanet J Rare Dis. 2015;10:134.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kuang SQ, Medina-Martinez O, Guo DC, et al. FOXE3 mutations predispose to thoracic aortic aneurysms and dissections. J Clin Invest. 2016;126:948–61.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Guo DC, Gong L, Regalado ES, et al. MAT2A mutations predispose individuals to thoracic aortic aneurysms. Am J Hum Genet. 2015;96:170–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Pannu H, Tran-Fadulu V, Papke CL, et al. MYH11 mutations result in a distinct vascular pathology driven by insulin-like growth factor 1 and angiotensin II. Hum Mol Genet. 2007;16:2453–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wang L, Guo DC, Cao J, et al. Mutations in myosin light chain kinase cause familial aortic dissections. Am J Hum Genet. 2010;87:701–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. McKellar SH, Tester DJ, Yagubyan M, Majumdar R, Ackerman MJ, Sundt TM III. Novel NOTCH1 mutations in patients with bicuspid aortic valve disease and thoracic aortic aneurysms. J Thorac Cardiovasc Surg. 2007;134:290–6.

    Article  CAS  PubMed  Google Scholar 

  44. Proost D, Vandeweyer G, Meester JA, et al. Performant mutation Iientification using targeted next-generation sequencing of 14 thoracic aortic aneurysm genes. Hum Mutat. 2015;36:808–14.

    Article  CAS  PubMed  Google Scholar 

  45. Guo DC, Regalado E, Casteel DE, et al. Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections. Am J Hum Genet. 2013;93:398–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Doyle AJ, Doyle JJ, Bessling SL, et al. Mutations in the TGF-beta repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm. Nat Genet. 2012;44:1249–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Callewaert BL, Willaert A, Kerstjens-Frederikse WS, et al. Arterial tortuosity syndrome: clinical and molecular findings in 12 newly identified families. Hum Mutat. 2008;29:150–8.

    Article  CAS  PubMed  Google Scholar 

  48. Micha D, Guo DC, Hilhorst-Hofstee Y, et al. SMAD2 Mutations are associated with arterial aneurysms and dissections. Hum Mutat. 2015;36:1145–9.

    Article  CAS  PubMed  Google Scholar 

  49. van der Linde D, van de Laar IM, Bertoli-Avella AM, et al. Aggressive cardiovascular phenotype of aneurysms-osteoarthritis syndrome caused by pathogenic SMAD3 variants. J Am Coll Cardiol. 2012;60:397–403.

    Article  CAS  PubMed  Google Scholar 

  50. van de Laar IM, van der Linde D, Oei EH, et al. Phenotypic spectrum of the SMAD3-related aneurysms-osteoarthritis syndrome. J Med Genet. 2012;49:47–57.

    Article  PubMed  Google Scholar 

  51. Heald B, Rigelsky C, Moran R, et al. Prevalence of thoracic aortopathy in patients with juvenile Polyposis Syndrome-Hereditary Hemorrhagic Telangiectasia due to SMAD4. Am J Med Genet A. 2015;167A:1758–62.

    Article  CAS  PubMed  Google Scholar 

  52. Wain KE, Ellingson MS, McDonald J, et al. Appreciating the broad clinical features of SMAD4 mutation carriers: a multicenter chart review. Genet Med. 2014;16:588–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Gillis E, Kumar AA, Luyckx I, et al. Candidate gene resequencing in a large bicuspid aortic valve-associated thoracic aortic aneurysm cohort: SMAD6 as an important contributor. Front Physiol. 2017;8:400.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Lindsay ME, Schepers D, Bolar NA, et al. Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. Nat Genet. 2012;44:922–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Boileau C, Guo DC, Hanna N, et al. TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome. Nat Genet. 2012;44:916–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Renard M, Callewaert B, Malfait F, et al. Thoracic aortic-aneurysm and dissection in association with significant mitral valve disease caused by mutations in TGFB2. Int J Cardiol. 2013;165:584–7.

    Article  PubMed  Google Scholar 

  57. Bertoli-Avella AM, Gillis E, Morisaki H, et al. Mutations in a TGF-beta ligand, TGFB3, cause syndromic aortic aneurysms and dissections. J Am Coll Cardiol. 2015;65:1324–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. MacCarrick G, Black JH III, Bowdin S, et al. Loeys-Dietz syndrome: a primer for diagnosis and management. Genet Med. 2014;16:576–87.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Jondeau G, Ropers J, Regalado E, et al. International registry of patients carrying TGFBR1 or TGFBR2 mutations: results of the MAC (Montalcino Aortic Consortium). Circ Cardiovasc Genet. 2016;9:548–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Boodhwani M, Andelfinger G, Leipsic J, et al. Canadian Cardiovascular Society position statement on the management of thoracic aortic disease. Can J Cardiol. 2014;30:577–89.

    Article  PubMed  Google Scholar 

  61. Isselbacher EM, Lino Cardenas CL, Lindsay ME. Hereditary influence in thoracic aortic aneurysm and dissection. Circulation. 2016;133:2516–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Regalado ES, Guo DC, Santos-Cortez RL, et al. Pathogenic FBN1 variants in familial thoracic aortic aneurysms and dissections. Clin Genet. 2016;89:719–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Weinsaft JW, Devereux RB, Preiss LR, et al. Aortic dissection in patients with genetically mediated aneurysms: incidence and predictors in the genTAC registry. J Am Coll Cardiol. 2016;67:2744–54.

    Article  PubMed  PubMed Central  Google Scholar 

  64. den Hartog AW, Franken R, Zwinderman AH, et al. The risk for type B aortic dissection in Marfan syndrome. J Am Coll Cardiol. 2015;65:246–54.

    Article  Google Scholar 

  65. Baudhuin LM, Kotzer KE, Lagerstedt SA. Increased frequency of FBN1 truncating and splicing variants in Marfan syndrome patients with aortic events. Genet Med. 2015;17:177–87.

    Article  CAS  PubMed  Google Scholar 

  66. Franken R, Groenink M, de Waard V, et al. Genotype impacts survival in Marfan syndrome. Eur Heart J. 2016;37:3285–90.

    Article  CAS  PubMed  Google Scholar 

  67. Franken R, den Hartog AW, Radonic T, et al. Beneficial outcome of losartan therapy depends on type of FBN1 mutation in Marfan syndrome. Circ Cardiovasc Genet. 2015;8:383–8.

    Article  CAS  PubMed  Google Scholar 

  68. Tran-Fadulu V, Pannu H, Kim DH, et al. Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations. J Med Genet. 2009;46:607–13.

    Article  CAS  PubMed  Google Scholar 

  69. Attias D, Stheneur C, Roy C, et al. Comparison of clinical presentations and outcomes between patients with TGFBR2 and FBN1 mutations in Marfan syndrome and related disorders. Circulation. 2009;120:2541–9.

    Article  CAS  PubMed  Google Scholar 

  70. Pepin MG, Schwarze U, Rice KM, Liu M, Leistritz D, Byers PH. Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV). Genet Med. 2014;16:881–8.

    Article  CAS  PubMed  Google Scholar 

  71. Pepin MG, Murray ML, Byers PH. Vascular Ehlers-Danlos Syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews(R). Seattle (WA) 1993.

  72. Shalhub S, Black JH III, Cecchi AC, et al. Molecular diagnosis in vascular Ehlers-Danlos syndrome predicts pattern of arterial involvement and outcomes. J Vasc Surg. 2014;60:160–9.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Frank M, Albuisson J, Ranque B, et al. The type of variants at the COL3A1 gene associates with the phenotype and severity of vascular Ehlers-Danlos syndrome. Eur J Hum Genet. 2015;23:1657–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Gillis E, Van Laer L, Loeys BL. Genetics of thoracic aortic aneurysm: at the crossroad of transforming growth factor-beta signaling and vascular smooth muscle cell contractility. Circ Res. 2013;113:327–40.

    Article  CAS  PubMed  Google Scholar 

  75. Milewicz DM, Regalado ES. Use of genetics for personalized management of heritable thoracic aortic disease: how do we get there? J Thorac Cardiovasc Surg. 2015;149:S3–5.

    Article  PubMed  Google Scholar 

  76. Morisaki H, Akutsu K, Ogino H, et al. Mutation of ACTA2 gene as an important cause of familial and nonfamilial nonsyndromatic thoracic aortic aneurysm and/or dissection (TAAD). Hum Mutat. 2009;30:1406–11.

    Article  CAS  PubMed  Google Scholar 

  77. Regalado ES, Guo DC, Prakash S, et al. Aortic disease presentation and outcome Associated With ACTA2 Mutations. Circ Cardiovasc Genet. 2015;8:457–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Guo DC, Papke CL, Tran-Fadulu V, et al. Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease. Am J Hum Genet. 2009;84:617–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Milewicz DM, Ostergaard JR, Ala-Kokko LM, et al. De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction. Am J Med Genet A. 2010;152A:2437–43.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Iakoubova OA, Tong CH, Rowland CM, et al. Genetic variants in FBN-1 and risk for thoracic aortic aneurysm and dissection. PloS one. 2014;9:e91437.

    Article  PubMed  PubMed Central  Google Scholar 

  81. LeMaire SA, McDonald ML, Guo DC, et al. Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1. Nat Genet. 2011;43:996–1000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Iakoubova OA, Tong CH, Catanese J, et al. KIF6 719Arg Genetic variant and risk for thoracic aortic dissection. Aorta (Stamford). 2016;4:83–90.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Guo DC, Grove ML, Prakash SK, et al. Genetic Variants in LRP1 and ULK4 Are Associated with Acute Aortic Dissections. Am J Hum Genet. 2016;99:762–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Prakash S, Kuang SQ, Gen TACRI, Regalado E, Guo D, Milewicz D. Recurrent rare genomic copy number variants and bicuspid aortic valve are enriched in early onset thoracic aortic aneurysms and dissections. PloS one. 2016;11:e0153543.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Landis BJ, Schubert JA, Lai D, et al. Exome sequencing identifies candidate genetic modifiers of syndromic and familial thoracic aortic aneurysm severity. J Cardiovasc Transl Res. 2017;10:423–32.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Campens L, Callewaert B, Muino Mosquera L, et al. Gene panel sequencing in heritable thoracic aortic disorders and related entities - results of comprehensive testing in a cohort of 264 patients. Orphanet J Rare Dis. 2015;10:9.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Schubert JA, Landis BJ, Shikany AR, Hinton RB, Ware SM. Clinically relevant variants identified in thoracic aortic aneurysm patients by research exome sequencing. Am J Med Genet A. 2016;170A:1288–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Wooderchak-Donahue W, VanSant-Webb C, Tvrdik T, et al. Clinical utility of a next generation sequencing panel assay for Marfan and Marfan-like syndromes featuring aortopathy. Am J Med Genet A. 2015;167A:1747–57.

    Article  CAS  PubMed  Google Scholar 

  89. Yang H, Luo M, Fu Y, et al. Genetic testing of 248 Chinese aortopathy patients using a panel assay. Sci Rep. 2016;6:33002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Poninska JK, Bilinska ZT, Franaszczyk M, et al. Next-generation sequencing for diagnosis of thoracic aortic aneurysms and dissections: diagnostic yield, novel mutations and genotype phenotype correlations. J Transl Med. 2016;14:115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Ziganshin BA, Bailey AE, Coons C, et al. Routine genetic testing for thoracic aortic aneurysm and dissection in a clinical setting. Ann Thorac Surg. 2015;100:1604–11.

    Article  PubMed  Google Scholar 

  92. Ziganshin BA ,Bailey AE, Brownstein A, Tranquilli M, Bale AE, Elefteriades JA. Identification of genetic defects causing thoracic aortic aneurysm by whole exome sequencing: experience in 211 patients. Available online: https://www.meetingswesternthoracicorg/abstracts/2017/CF3cgi. 2017.

  93. Wang Y, Barbacioru CC, Shiffman D, et al. Gene expression signature in peripheral blood detects thoracic aortic aneurysm. PloS one. 2007;2:e1050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

None of the authors received funding in preparation of this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John Alex Elefteriades.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brownstein, A.J., Ziganshin, B.A. & Elefteriades, J.A. Human aortic aneurysm genomic dictionary: is it possible?. Indian J Thorac Cardiovasc Surg 35 (Suppl 2), 57–66 (2019). https://doi.org/10.1007/s12055-018-0659-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12055-018-0659-6

Keywords

Navigation