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

BMC Medical Genetics

Gian Franco Gensini⁵  Magdi Yacoub³  Robert O Bonow⁴  Rosanna Abbate¹  Cristina Porciani¹  Monica Attanasio¹  Elena Sticchi¹  Betti Giusti¹  Stefano Nistri²  Guglielmina Pepe¹ 

[1] Department of Heart and Vessels, Regional Marfan Syndrome and Related Disorders Center, Careggi Hospital, Florence, Italy;Cardiology Service, CMSR Veneto Medica, AltavillaVicentina, Italy;Heart Science Centre, Imperial College, London, UK;Department of Medicine, Northwestern University, Chicago, IL, USA;S. Maria agli Ulivi Center, Fondazione Don Carlo Gnocchi, Onlus, IRCCS, Florence, Italy

关键词: Fibrillin-1;    Marfan syndrome;    Aneurysm;    Aortic disease;    Bicuspid aortic valve;   

Others  :  1092511
DOI  :  10.1186/1471-2350-15-23

 received in 2013-12-12, accepted in 2014-02-14,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Pepe et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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