Postmortem diagnosis of Marfan syndrome in a case of sudden death due to aortic rupture: Detection of a novel FBN1 frameshift mutation
Postmortem diagnosis of Marfan syndrome in a case of sudden death due to aortic rupture: Detection of a novel FBN1 frameshift mutation
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DOI：
10.1016/j.forsciint.2016.02.013
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发表时间：
2016-04-01
影响因子：
2.2
通讯作者：
Liu, Qian
中科院分区：
文献类型：
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作者：
Wang, Yunyun;Chen, Shu;Liu, Qian
为调查1例36岁中国男性猝死的原因，采用法医学尸检方法，结合法医病理学检查和基因测序分析，确定死因。从血液中提取基因组DNA样品并进行高通量测序。主要发现包括主动脉根部扩张，主动脉破裂和夹层，随后心包填塞。此外，还观察到蜘蛛爪和其他骨骼畸形。通过对FBN-1基因（FBN 1）进行测序，发现了五种遗传变异，包括四种先前已知的单核苷酸多态性（SNP）和一种新的移码突变，从而诊断为马凡氏综合征。在外显子40中检测到的移码突变（c.4921delG，p.glu1641llysFsX9）导致在接下来的8个氨基酸之后的终止密码子。这4个SNP包括一个剪接位点突变（c.3464-5 G > A，rs 11853943）、一个同义突变（p.Asn625Asn，rs 25458）和两个错义突变（p.Pro1148Ala，rs 140598; p.Cys472Tyr，rs 4775765）。建议对亲属进行基因筛查，因为据报道，死者的父亲和兄弟分别在40岁和25岁时死于突发性心力衰竭。死者的儿子缺乏相关的突变。本文强调法医学尸检分析在马凡氏综合征分子发病机制研究和高危亲属早期诊断中的重要作用。(C)2016爱思唯尔爱尔兰有限公司版权所有。
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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.