title: Identification of fibrillin 1 gene mutations in patients with bicuspid aortic valve (BAV) without Marfan syndrome.
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.
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Critical Medical Care and Medical Specialities; DENOTHE Center, University of Florence, Largo Brambilla 3, 50134 Florence, Italy. guglielmina.pepe@unifi.it.
authors.forename: Guglielmina
authors.initials: G
authors.lastname: Pepe
authors.forename: Stefano
authors.initials: S
authors.lastname: Nistri
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
authors.forename: Elena
authors.initials: E
authors.lastname: Sticchi
authors.forename: Monica
authors.initials: M
authors.lastname: Attanasio
authors.forename: Cristina
authors.initials: C
authors.lastname: Porciani
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.forename: Robert O
authors.initials: RO
authors.lastname: Bonow
authors.forename: Magdi
authors.initials: M
authors.lastname: Yacoub
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Gensini
mesh_terms: D000328:Adult; D000784:Aortic Dissection / Q000000981:diagnostic imaging / Q000235:genetics; D001011:Aorta / Q000473:pathology; D001014:Aortic Aneurysm / Q000000981:diagnostic imaging / Q000235:genetics; D001021:Aortic Valve / Q000002:abnormalities* / Q000000981:diagnostic imaging; D001483:Base Sequence; D000082882:Bicuspid Aortic Valve Disease; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004108:Dilatation, Pathologic / Q000000981:diagnostic imaging / Q000235:genetics; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006349:Heart Valve Diseases / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D025202:Molecular Diagnostic Techniques; D020125:Mutation, Missense; D014463:Ultrasonography; D055815:Young Adult; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines