ABSTRACT
Objective To detect 14 genes including fibrillin-1(FBN1) and so on mutations in 17 patients with Marfan syndrome(MFS) and family members of 2 patients and to investigate the correlation between FBN1 gene mutation and MFS.Methods Genomic DNAs were extracted from whole blood sample of 17 patients and 43 family members.After DNA samples were amplified by polymerase chain raction(PCR), we used capture panels to get target genes which would be sequenced by Illumina HiSeq2500 Analyzers(Illumina, SanDiego, USA).The target genes included ACTA2、CBS、FBN1、FBN2、MYH11、COL3A1、SMAD3、TGFBR1、TGFBR2、MYLK、MSTN、COLA2、TGFB2 and SLC2A10.The results of sequencing would be compared with multiple databases, including NCBI dbSNP, HapMap, 1000 human genome dataset and database of 100 Chinese healthy adults, to find gene mutation.Finally, these mutations would be validated using conventional Sanger sequencing methods.Results A total of 10 FBN1 mutations and 1 actin alpha2(ACTA2) mutation in 17 patients were identified, of which 8 FBN1 mutations and 1 ACTA2 mutation were novel.One FBN1 mutation was underwent family investigation and we found in this family, all patients had this mutation and others did not have it.Conclusion Missense mutation of c.7280G>A in the 59th exon of FBN1 gene is new pathogenic mutation for MFS.The other 8 novel mutations may be the pathogenic factors of MFS.