Next-generation sequencing identifies novel mutations in the FBN1 gene for two Chinese families with Marfan syndrome

Marfan syndrome (MFS) is an autosomal dominant heterogeneous disorder of connective tissue characterized by the early development of thoracic aneurysms/dissections, together with defects of the ocular and skeletal systems. Loss-of-function mutations in fibrillin-1 (FBN1) encoded by the gene, FBN1 (MFS-1), and in the transforming growth factor β receptor 2 (TGFBR2) gene, TGFBR2 (MFS-2), are major causes of this disorder. In the present study, a rapid and cost-effective method for genetically diagnosing MFS was described and used to identify disease-causing mutations in two unrelated pedigrees with MFS in mainland China. Using targeted semiconductor sequencing, two pathogenic mutations in four MFS patients of the two pedigrees were identified, including a novel frameshift insertion, p.G2120fsX2160, and a reported nonsense mutation, p.Arg529X (rs 137854476), in the FBN1 gene. In addition, a rare, probably benign Chinese-specific polymorphism in the FBN1 gene was also revealed.