Biochemical and Biophysical Research Communications
Novel missense mutations (p.T596M and p.P1797H) in NOTCH1 in patients with bicuspid aortic valve
Section snippets
Material and methods
DNA samples. Genomic DNA was extracted from peripheral blood cells or calcified aortic tissues obtained during aortic valve replacement surgery from 48 patients with BAV (mean age 53.4 ± 13.9 years; 40 male/8 female) using the QIAamp DNA Mini-Kit according to the manufacturer’s recommendations (Qiagen, Hilden, Germany). All patients were clinically evaluated for evidence of BAV, classified as fusion of right-coronary, left-coronary leaflets (77.1%), and others (22.9%). Clinical characteristics of
Results
We re-sequenced all 34 coding exons including adjacent intronic as well as 5′ and 3′ untranslated sequences from the human NOTCH1 gene in 48 patients with sporadic BAV in order to screen for NOTCH1 variants that might cause BAV.
In total we identified 57 heterozygous variants in the analyzed patients (Table 3). Twenty-one sequence variants are located within exons and 36 within intronic or 5′-UTR sequences. Thirty-five variants were described previously as polymorphisms. The remaining 22,
Discussion
The importance of genetic factors involved in the development of aortic valve disease has become more apparent. Recently, the most common congenital cardiac malformation, the bicuspid aortic valve (BAV), was described as a genetic disorder, which occurs in 1–2% of the general population [2], [7], [9], [15], [16]. Recently, Garg et al., reported mutations in NOTCH1 gene in two families with BAV (R1108X; H1505del) that were associated with the calcification phenotype in BAV [13]. The study by
Acknowledgments
We are grateful to all our patients with BAV for their help and contribution to this study. This work was done in collaborations supported by: Deutsche Forschungsgemeinschaft (Schu672/9-1, Schu672/10-1, Schu672/12-1, and Schu672/14-1) and Bundesministerium für Bildung und Forschung (National Genome Network 2 (01GS0418) H.S., J.E.).
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Both authors are equal to this work.