BackgroundBicuspid 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.MethodsTen 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.ResultsWe 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.ConclusionsThe 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.

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Italian (Calabria) 96 43 .448 ‫ע‬ .051 Spanish a 66 36 .545 ‫ע‬ .061 Sub-Saharan African: Dendi 24 0 0 Bariba 26 2 .077 ‫ע‬ .052 Berba 32 3 .094 ‫ע‬ .051 Fon 96 8 .083 ‫ע‬ .028 Total b 178 13 .073 ‫ע‬ .019 Asian: Tharu a 108 21 .194 ‫ע‬ .038 Chinese a 24 9 .375 ‫ע‬ .099 Indonesian 98 2 .020 ‫ע‬ .014 Amerindian: Cayapa a 114 49 .430 ‫ע‬ .046 Mixed: Ethiopian: Amhara 54 4 .074 ‫ע‬ .033 Oromo 54 3 .055 ‫ע‬ .031 Total b 108 7 .065 ‫ע‬ .024 African Ecuadoran: Viche a 82 13 .183 ‫ע‬ .043 a Testable population, except for Calabrians (Italy), in Hardy-Weinberg equilibrium. b Populations were pooled when compatibility was verified by a x 2 test of heterogeneity.