FBN1 gene mutation characteristics and clinical features for the prediction of mitral valve disease progression

Int J Cardiol. 2013 Sep 30;168(2):953-9. doi: 10.1016/j.ijcard.2012.10.044. Epub 2012 Nov 22.


Background: Until today, FBN1 gene mutation characteristics were not compared with clinical features for the prediction of mitral valve disease progression.

Methods: Therefore, we conducted a study of 116 patients (53 men, 63 women aged 33 ± 15 years) with a causative FBN1 gene mutation and ≤ moderate mitral valve regurgitation at baseline.

Results: During 7.4 ± 6.8 years 30 patients developed progression of mitral valve regurgitation ≥ 1 grade (primary endpoint), and 26 patients required mitral valve surgery (secondary endpoint). Cox regression analysis identified an association of atrial fibrillation (hazard ratio (HR)=2.703; 95% confidence interval (CI) 1.013-7.211; P=.047), left ventricular ejection fraction (HR=.970; 95%CI .944-.997; P=.032), indexed end-diastolic left ventricular diameter (HR=15.165; 95%CI 4.498-51.128; P<.001), indexed left atrial diameter (HR=1.107; 95%CI 1.045-1.173; P=.001), tricuspid valve prolapse (HR=2.599; 95%CI 1.243-5.437; P=.011), posterior leaflet prolapse (HR=1.075; 95%CI 1.023-1.130; P=.009), and posterior leaflet thickening (HR=3.368; 95%CI 1.265-8.968; P=.015) with progression of mitral valve disease, whereas none of the FBN1 gene mutation characteristics were associated with progression of mitral valve disease. However, Cox regression analysis identified a marginal relationship of FBN1 gene mutations located both in a transforming-growth-factor beta-binding protein-like (TGFb-BP) domain (HR=3.453; 95%CI .982-12.143; P=.053), and in the calcium-binding epidermal growth factor-like (cbEGF) domain (HR=2.909; 95%CI .957-8.848; P=.060) with mitral valve surgery, a finding that was corroborated by Kaplan-Meier analysis (P=.014; and P=.041, respectively).

Conclusion: Clinical features were better predictors of mitral valve disease progression than FBN1 gene mutation characteristics.

Keywords: FBN1; Genotype; Marfan syndrome; Mitral valve prolapse; Prediction.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Disease Progression*
  • Female
  • Fibrillin-1
  • Fibrillins
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Microfilament Proteins / genetics*
  • Middle Aged
  • Mitral Valve Insufficiency / diagnosis*
  • Mitral Valve Insufficiency / genetics*
  • Mitral Valve Insufficiency / pathology
  • Mutation / genetics*
  • Young Adult


  • FBN1 protein, human
  • Fibrillin-1
  • Fibrillins
  • Microfilament Proteins