Mutation screening in the FBN1 gene responsible for Marfan syndrome and related disorder in Chinese families

Background Previous studies showed that the fibrillin-1 gene (FBN1) is responsible for Marfan sydrome (MFS) pathogenesis. This study is conducted to screen for mutations in the FBN1 gene in Chinese families with MFS. Methods Eight families with MFS and related disorder were recruited in this study. All available family members underwent complete physical, ophthalmic, and cardiovascular examination. Mutation screening was performed using targeted next-generation sequencing. Candidate variants were amplified by polymerase chain reaction and verified by direct Sanger sequencing. Results Four novel heterozygous mutations in FBN1, including c.2861G>T (p.R954L), c.4087G>A (p.D1363N), c.4987T>G (p.C1663G), and c.5032T>G (p.Y1678D), as well as four known mutations, c.3617G>A (p.G1206D), c.4460A>G (p.D1487G), c.4588C>T (p.R1530C), and c.718C>T (p.R240C) were identified. Affected patients from each family were found to carry one of the mutations, whereas the unaffected members and 1,086 normal controls were not. Each mutation was found to be cosegregated with MFS phenotype and related disorder in each family. Multiple sequence alignment of the human fibrillin-1 protein showed that these mutations occurred in a highly conserved region among different species. Conclusions Eight FBN1 mutations were identified in Chinese families with MFS and related disorder. These data expands FBN1 mutation spectrum and further emphasizes the role of FBN1 in the pathogenesis of MFS.