FBN1 mutations largely contribute to sporadic non-syndromic aortic dissection

• Published in: Human molecular genetics 2017-12, Vol.26 (24), p.4814-4822
• Main Authors: Tan, Lun, Li, Zongze, Zhou, Chengming, Cao, Yanyan, Zhang, Lina, Li, Xianqing, Cianflone, Katherine, Wang, Yan, Wang, Dao Wen
• Format: Article
• Language: English
• Subjects: Adult; Aneurysm, Dissecting - genetics; Aortic Aneurysm, Thoracic - genetics; Base Sequence; Female; Fibrillin-1 - genetics; Genetic Predisposition to Disease; Genotype; Humans; Male; Marfan Syndrome - genetics; Microfilament Proteins - genetics; Middle Aged; Mutation; Odds Ratio
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddx360

Mutations in FBN1 have been well identified in syndromic aortic dissection (AD) and familial thoracic aortic aneurysms and dissections. However, whether mutations of FBN1 contribute to sporadic non-syndromic AD and the characteristics of mutations remain unknown. Using next-generation-sequencing technology, FBN1 was sequenced in a total of 702 sporadic cases (including 687 of non-syndromic AD and 15 of sporadic Marfan syndrome with aortic event, and 527 normal controls). For the sporadic non-syndromic AD cohort, we found 26 variants in 27 patients (18 with missense, 2 frameshift, 1 initiation codon mutation, 3 nonsense and 3 splice site mutations). The prevalence of variants was significantly high in the sporadic non-syndromic AD cohort (27/687, 3.9%). The patients with FBN1 mutations were younger, suffered from fewer risk factors such as hypertension and smoking, and were less gender partitioned than non-FBN1-mutation AD patients. The mutations were spread along the FBN1 gene in our sporadic non-syndromic AD cohort and mutation locations are not different between non-syndromic and syndromic patients. These results demonstrate that the deleterious mutations in FBN1 largely contribute to pathogenesis of sporadic non-syndromic AD, which expands our knowledge of FBN1 variants and the genetic basis and pathology of AD.