Genetics of hereditary large vessel diseases

J Hum Genet. 2016 Jan;61(1):21-6. doi: 10.1038/jhg.2015.119. Epub 2015 Oct 8.

Abstract

Recent progress in the study of hereditary large vessel diseases such as Marfan syndrome (MFS) have not only identified responsible genes but also provided better understanding of the pathophysiology and revealed possible new therapeutic targets. Genes identified for these diseases include FBN1, TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3, SKI, EFEMP2, COL3A1, FLNA, ACTA2, MYH11, MYLK and SLC2A10, as well as others. Their dysfunction disrupts the function of transforming growth factor-β (TGF-β) signaling pathways, as well as that of the extracellular matrix and smooth muscle contractile apparatus, resulting in progression of structural damage to large vessels, including aortic aneurysms and dissections. Notably, it has been shown that the TGF-β signaling pathway has a key role in the pathogenesis of MFS and related disorders, which may be important for development of strategies for medical and surgical treatment of thoracic aortic aneurysms and dissections.

Publication types

  • Review

MeSH terms

  • Aortic Aneurysm, Thoracic / drug therapy
  • Aortic Aneurysm, Thoracic / etiology
  • Aortic Aneurysm, Thoracic / genetics*
  • Aortic Dissection / drug therapy
  • Aortic Dissection / etiology
  • Aortic Dissection / genetics*
  • Ehlers-Danlos Syndrome / genetics
  • Fibrillin-1 / genetics
  • Humans
  • Loeys-Dietz Syndrome / genetics
  • Marfan Syndrome / genetics*
  • Mutation
  • Signal Transduction / genetics
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / physiology

Substances

  • FBN1 protein, human
  • Fibrillin-1
  • Transforming Growth Factor beta