Application of Whole Exome Sequencing and Functional Annotations to Identify Genetic Variants Associated with Marfan Syndrome

Marfan syndrome (MFS) is a rare disease that affects connective tissue, which causes abnormalities in several organ systems including the heart, eyes, bones, and joints. The autosomal dominant disorder was found to be strongly associated with FBN1, TGFBR1, and TGFBR2 mutations. Although multiple genetic mutations have been reported, data from Asian populations are still limited. As a result, we utilized the whole exome sequencing (WES) technique to identify potential pathogenic variants of MFS in a Taiwan cohort. In addition, a variety of annotation databases were applied to identify the biological functions as well as the potential mechanisms of candidate genes. In this study, we confirmed the pathogenicity of FBN1 to MFS. Our results indicated that TTN and POMT1 may be likely related to MFS phenotypes. Furthermore, we found nine unique variants highly shared in a MFS family cohort, of which eight are novel variants worthy of further investigation.

Automated summary

Marfan syndrome is a rare disease that affects multiple organ systems. This study identified potential pathogenic genes associated with MFS using whole exome sequencing in a Taiwan cohort, and also discovered novel candidate genes. The findings contribute to a better understanding of the pathogenesis of MFS.