LAUSR

BACKGROUND Marfan syndrome is a hereditary connective tissue disease accompanied by autosomal dominant inheritance; that mainly arises from a mutation in the fibrillin-1 gene (FBN1). Aortic dissection and rupture are the common and lethal complications of MFS and may cause sudden unexpected death. METHOD A man aged 34 was admitted to the hospital due to persistent pain in his abdomen 12 h post-drinking and suddenly died 10 h later. A forensic autopsy was performed to identify the underlying mechanism of death. Due to the high suspected of MFS, Sanger sequencing was performed, and a novel mutation was detected in the deceased. To clarify the underlying mechanism of this mutation, real-time quantitative polymerase chain reaction was conducted and Western blot analysis was performed in vitro. RESULTS A novel PTC mutation c.933C > A in FBN1 was found. Through family history inspection and Sanger sequencing, other MFS patients in the present family were confirmed. The pathologic changes in the aorta in the present case showed media cystic degeneration, disordered arrangement of elastic fibers and a significant reduction in fibrillin 1 compared with the control. The mutation led to significant reduction inFBN1 mRNA and fibrillin-1 in cells in vitro, and overexpression of phospho-Smad2 was observed. CONCLUSION We confirmed a novel pathogenic PTC mutation in the FBN1gene through Sanger sequencing, and the pathological changes and underlying mechanisms were also identified. The present work not only extends the pathogenic mutation spectrum of MFS, but also stresses the role of forensic autopsy, genetic analysis and functional validation of novel mutations in cases of sudden death associated with congenital diseases.