Exome sequencing identified a novel SMAD2 mutation in a Chinese family with early onset aortic aneurysms.

Aortic aneurysm remains a devastating disease due to its fatal complications, such as aortic dissection and rupture. A subset of aortic aneurysm is caused by genetic defect and to date more than a dozen of disease-causing genes have been discovered to account for the disease. In this study, by using whole exome sequencing, we identified a novel heterozygous missense mutation (c.833C>T, p.A278V) in the SMAD2 gene in a family with early onset aortic aneurysms. The mutation segregated in this family, was high conserved among species and predicted to be pathogenic by multiple in silico programs. To our knowledge, this is the second report that link the SMAD2 mutations to aortic aneurysm. We recommend that SMAD2 should be included in the expanding panel of genetic testing for patients with unexplained aortic aneurysms, which will facilitate genotype-phenotype correlation of SMAD2 mutations. Given the current wide application of molecular diagnosis in clinical setting, identification of the defected gene allows recognition of additional family members at risk for aortic diseases and gene-based management of the carriers.