Identification of fibrillin 1 gene mutations in patients with bicuspid aortic valve (BAV) without Marfan syndrome

Guglielmina Pepe*, Stefano Nistri, Betti Giusti, Elena Sticchi, Monica Attanasio, Cristina Porciani, Rosanna Abbate, Robert O. Bonow, Magdi Yacoub, Gian F. Gensini

*Corresponding author for this work

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Background: Bicuspid aortic valve (BAV) is the most frequent congenital heart disease with frequent involvement in thoracic aortic dilatation, aneurysm and dissection. Although BAV and Marfan syndrome (MFS) share some clinical features, and some MFS patients with BAV display mutations in FBN1, the gene encoding fibrillin-1, the genetic background of isolated BAV is poorly defined.Methods: Ten consecutive BAV patients [8 men, age range 24-42 years] without MFS were clinically characterized. BAV phenotype and function, together with evaluation of aortic morphology, were comprehensively assessed by Doppler echocardiography. Direct sequencing of each FBN1 exon with flanking intron sequences was performed on eight patients.Results: We detected three FBN1 mutations in two patients (aged 24 and 25 years) displaying aortic root aneurysm ≥50 mm and moderate aortic regurgitation. In particular, one patient had two mutations (p.Arg2726Trp and p.Arg636Gly) one of which has been previously associated with variable Marfanoid phenotypes. The other patient showed a pArg529Gln substitution reported to be associated with an incomplete MFS phenotype.Conclusions: The present findings enlarge the clinical spectrum of isolated BAV to include patients with BAV without MFS who have involvement of FBN1 gene. These results underscore the importance of accurate phenotyping of BAV aortopathy and of clinical characterization of BAV patients, including investigation of systemic connective tissue manifestations and genetic testing.

Original languageEnglish (US)
Article number23
JournalBMC Medical Genetics
Volume15
Issue number1
DOIs
StatePublished - Feb 24 2014

Keywords

  • Aneurysm
  • Aortic disease
  • Bicuspid aortic valve
  • Fibrillin-1
  • Marfan syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Pepe, G., Nistri, S., Giusti, B., Sticchi, E., Attanasio, M., Porciani, C., Abbate, R., Bonow, R. O., Yacoub, M., & Gensini, G. F. (2014). Identification of fibrillin 1 gene mutations in patients with bicuspid aortic valve (BAV) without Marfan syndrome. BMC Medical Genetics, 15(1), [23]. https://doi.org/10.1186/1471-2350-15-23