Postmortem diagnosis of Marfan syndrome in a case of sudden death due to aortic rupture: Detection of a novel FBN1 frameshift mutation

Yunyun Wang; Shu Chen; Rongshuai Wang; Sizhe Huang; Mingzhen Yang; Liang Liu; Qian Liu

doi:10.1016/j.forsciint.2016.02.013

Postmortem diagnosis of Marfan syndrome in a case of sudden death due to aortic rupture: Detection of a novel FBN1 frameshift mutation

Forensic Sci Int. 2016 Apr:261:e1-4. doi: 10.1016/j.forsciint.2016.02.013.

Authors

Yunyun Wang¹, Shu Chen², Rongshuai Wang¹, Sizhe Huang¹, Mingzhen Yang¹, Liang Liu³, Qian Liu⁴

Affiliations

¹ Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
² Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
³ 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.
⁴ Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: caixe_liu0222@tom.com.

PMID: 26905825
DOI: 10.1016/j.forsciint.2016.02.013

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.

Keywords: Autopsy; FBN1; Frameshift mutation; Marfan syndrome.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aortic Rupture / etiology
Aortic Rupture / pathology
Asian People
China
Death, Sudden / etiology*
Fibrillin-1 / genetics*
Forensic Genetics
Forensic Pathology
Frameshift Mutation*
High-Throughput Nucleotide Sequencing
Humans
Male
Marfan Syndrome / diagnosis
Marfan Syndrome / genetics*
Polymorphism, Single Nucleotide

Substances

FBN1 protein, human
Fibrillin-1