SMAD2 Mutations Are Associated with Arterial Aneurysms and Dissections

Hum Mutat. 2015 Dec;36(12):1145-9. doi: 10.1002/humu.22854. Epub 2015 Sep 10.

Abstract

We report three families with arterial aneurysms and dissections in which variants predicted to be pathogenic were identified in SMAD2. Moreover, one variant occurred de novo in a proband with unaffected parents. SMAD2 is a strong candidate gene for arterial aneurysms and dissections given its role in the TGF-β signaling pathway. Furthermore, although SMAD2 and SMAD3 probably have functionally distinct roles in cell signaling, they are structurally very similar. Our findings indicate that SMAD2 mutations are associated with arterial aneurysms and dissections and are in accordance with the observation that patients with pathogenic variants in genes encoding proteins involved in the TGF-β signaling pathway exhibit arterial aneurysms and dissections as key features.

Keywords: SMAD2; TGF-ß; aneurysm; dissection.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alleles
  • Aneurysm / diagnosis
  • Aneurysm / genetics*
  • Aneurysm / metabolism
  • Aneurysm, Dissecting / diagnosis
  • Aneurysm, Dissecting / genetics*
  • Aneurysm, Dissecting / metabolism
  • Arteries / metabolism*
  • Arteries / pathology*
  • Computational Biology / methods
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Models, Molecular
  • Mutation*
  • Protein Interaction Domains and Motifs
  • Sequence Analysis, DNA
  • Smad2 Protein / chemistry
  • Smad2 Protein / genetics*
  • Young Adult

Substances

  • Smad2 Protein