Confirmation of Cause and Manner of Death Via a Comprehensive Cardiac Autopsy Including Whole Exome Next-Generation Sequencing

被引:36
作者
Loporcaro, Christina G. [1 ]
Tester, David J. [2 ,7 ]
Maleszewski, Joseph J. [3 ]
Kruisselbrink, Teresa [4 ]
Ackerman, Michael J. [2 ,5 ,6 ,7 ]
机构
[1] Mayo Clin & Mayo Fdn, Mayo Med Sch, Rochester, MN 55905 USA
[2] Mayo Clin, Dept Internal Med, Div Cardiovasc Dis, Rochester, MN 55905 USA
[3] Mayo Clin, Dept Lab Med & Pathol, Div Anat Pathol, Rochester, MN 55905 USA
[4] Mayo Clin, Dept Lab Med & Pathol, Div Lab Genet, Rochester, MN 55905 USA
[5] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA
[6] Mayo Clin, Dept Pediat & Adolescent Med, Div Pediat Cardiol, Rochester, MN 55905 USA
[7] Mayo Clin, Windland Smith Rice Sudden Death Genom Lab, Rochester, MN 55905 USA
关键词
FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; SUDDEN UNEXPLAINED DEATH; MOLECULAR AUTOPSY; MUTATIONS; CHILDREN;
D O I
10.5858/arpa.2013-0479-SA
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
100118 [医学信息学]; 100208 [临床检验诊断学];
摘要
Annually, the sudden death of thousands of young people remains inadequately explained despite medicolegal investigation. Postmortem genetic testing for channelopathies/cardiomyopathies may illuminate a potential cardiac mechanism and establish a more accurate cause and manner of death and provide an actionable genetic marker to test surviving family members who may be at risk for a fatal arrhythmia. Whole exome sequencing allows for simultaneous genetic interrogation of an individual's entire estimated library of approximately 30 000 genes. Following an inconclusive autopsy, whole exome sequencing and gene-specific surveillance of all known major cardiac channelopathy/cardiomyopathy genes (90 total) were performed on autopsy blood-derived genomic DNA from a previously healthy 16-year-old adolescent female found deceased in her bedroom. Whole exome sequencing analysis revealed a R249Q-MYH7 mutation associated previously with familial hypertrophic cardiomyopathy, sudden death, and impaired beta-myosin heavy chain (MHC-beta) actin-translocating and actin-activated ATPase (adenosine triphosphatase) activity. Whole exome sequencing may be an efficient and cost-effective approach to incorporate molecular studies into the conventional postmortem examination.
引用
收藏
页码:1083 / 1089
页数:7
相关论文
共 20 条
[1]
Ackerman MJ, 2011, HEART RHYTHM, V8, P1308, DOI [10.1016/j.hrthm.2011.05.020, 10.1093/europace/eur245]
[2]
TREAT: a bioinformatics tool for variant annotations and visualizations in targeted and exome sequencing data [J].
Asmann, Yan W. ;
Middha, Sumit ;
Hossain, Asif ;
Baheti, Saurabh ;
Li, Ying ;
Chai, High-Seng ;
Sun, Zhifu ;
Duffy, Patrick H. ;
Hadad, Ahmed A. ;
Nair, Asha ;
Liu, Xiaoyu ;
Zhang, Yuji ;
Klee, Eric W. ;
Kalari, Krishna R. ;
Kocher, Jean-Pierre A. .
BIOINFORMATICS, 2012, 28 (02) :277-278
[3]
Guidelines for autopsy investigation of sudden cardiac death [J].
Basso, Cristina ;
Burke, Margaret ;
Fornes, Paul ;
Gallagher, Patrick J. ;
de Gouveia, Rosa Henriques ;
Sheppard, Mary ;
Thiene, Gaetano ;
van der Wal, Allard .
VIRCHOWS ARCHIV, 2008, 452 (01) :11-18
[4]
Clarke L, 2012, NAT METHODS, V9, P1, DOI [10.1038/NMETH.1974, 10.1038/nmeth.1974]
[5]
Genetic predisposition to sudden cardiac death [J].
Crotti, Lia .
CURRENT OPINION IN CARDIOLOGY, 2011, 26 (01) :46-50
[6]
Posthumous diagnosis of long QT syndrome from neonatal screening cards [J].
Gladding, P. A. ;
Evans, C-A ;
Crawford, J. ;
Chung, S. K. ;
Vaughan, A. ;
Webster, D. ;
Neas, K. ;
Love, D. R. ;
Rees, M. I. ;
Shelling, A. N. ;
Skinner, J. R. .
HEART RHYTHM, 2010, 7 (04) :481-486
[7]
Progress With Genetic Cardiomyopathies Screening, Counseling, and Testing in Dilated, Hypertrophic, and Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy [J].
Hershberger, Ray E. ;
Cowan, Jason ;
Morales, Ana ;
Siegfried, Jill D. .
CIRCULATION-HEART FAILURE, 2009, 2 (03) :253-261
[8]
The emerging role of the cardiac genetic counselor [J].
Ingles, Jodie ;
Yeates, Laura ;
Semsarian, Christopher .
HEART RHYTHM, 2011, 8 (12) :1958-1962
[9]
Mapping short DNA sequencing reads and calling variants using mapping quality scores [J].
Li, Heng ;
Ruan, Jue ;
Durbin, Richard .
GENOME RESEARCH, 2008, 18 (11) :1851-1858
[10]
Fast and accurate short read alignment with Burrows-Wheeler transform [J].
Li, Heng ;
Durbin, Richard .
BIOINFORMATICS, 2009, 25 (14) :1754-1760