Impact of Pathogenic FBN1 Variant Types on the Progression of Aortic Disease in Patients With Marfan Syndrome

Circ Genom Precis Med. 2018 Jun;11(6):e002058. doi: 10.1161/CIRCGEN.117.002058.

Abstract

Background: Marfan syndrome can cause life-threatening aortic complications. We investigated the relationship between FBN1 genotype and severe aortopathy (aortic root replacement, type A dissections, and related death).

Methods: We evaluated 248 patients with pathogenic or likely pathogenic FBN1 variants. The variants were classified as haploinsufficient type (HI, n=93) or dominant-negative type (DN, n=155) based on their location and predicted amino acid alterations, and we examined the effects of the FBN1 genotype on severe aortic events (aortic root replacement, type A dissections, and related death).

Results: The cumulative event-free probability was significantly lower in the HI group than in the DN group (adjusted hazard ratio, 2.1; 95% confidence interval, 1.4 -3.2; P<0.001).

Conclusions: DN-CD+HI patients should be monitored more carefully than DN-nonCD patients for rapid development of aortic root aneurysms.

Keywords: Marfan syndrome; aneurysm; aneurysm, dissecting; aorta; humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aortic Diseases / complications
  • Aortic Diseases / genetics
  • Aortic Diseases / pathology*
  • Child
  • Child, Preschool
  • Disease Progression
  • Female
  • Fibrillin-1 / genetics*
  • Genes, Dominant
  • Genomics / methods*
  • Haploinsufficiency
  • Humans
  • Male
  • Marfan Syndrome / complications
  • Marfan Syndrome / genetics
  • Marfan Syndrome / pathology*
  • Middle Aged
  • Mutation*
  • Retrospective Studies
  • Severity of Illness Index
  • Young Adult

Substances

  • FBN1 protein, human
  • Fibrillin-1