title: Postmortem diagnosis of Marfan syndrome in a case of sudden death due to aortic rupture: Detection of a novel FBN1 frameshift mutation.
abstract: To investigate the sudden death of a 36-year-old Chinese man, a medicolegal autopsy was performed, combining forensic pathological examinations and genetic sequencing analysis to diagnose the cause of death. Genomic DNA samples were extracted from blood and subjected to high-throughput sequencing. Major findings included a dilated aortic root with a ruptured and dissected aorta and consequent tamponade of the pericardial sac. Moreover, arachnodactyly and other skeletal deformities were noted. By sequencing the fibrillin-1 gene (FBN1), five genetic variations were found, including four previously known single nucleotide polymorphisms (SNPs) and a novel frameshift mutation, leading to the diagnosis of Marfan syndrome. The frameshift mutation (c.4921delG, p.glu1641llysFsX9) detected in exon 40 led to a stop codon after the next 8 amino acids. The four SNPs included a splice site mutation (c.3464-5 G>A, rs11853943), a synonymous mutation (p.Asn625Asn, rs25458), and two missense mutations (p.Pro1148Ala, rs140598; p.Cys472Tyr, rs4775765). Genetic screening was recommended for the relatives as it was reported that the father and brother of the deceased had died at the ages of 40 and 25, respectively, from sudden cardiac failure. The son of the deceased lacked the relevant mutations. This report emphasizes the important contribution of medicolegal postmortem analysis on the molecular pathogenesis study of Marfan syndrome and early diagnosis of at-risk relatives.
authors.affiliation: Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Rongshuai
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Sizhe
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Mingzhen
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Evidence Science, China University of Political Science and Law, Ministry of Education, Beijing 100040, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: caixe_liu0222@tom.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000328:Adult; D001019:Aortic Rupture / Q000209:etiology / Q000473:pathology; D044466:Asian People; D002681:China; D003645:Death, Sudden / Q000209:etiology*; D000071838:Fibrillin-1 / Q000235:genetics*; D053803:Forensic Genetics; D049429:Forensic Pathology; D016368:Frameshift Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; C000605722:FBN1 protein, human; D054392:Adipokines
keywords: Autopsy; FBN1; Frameshift mutation; Marfan syndrome