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Arch Pathol Lab Med ; 138(8): 1083-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24298987

RESUMO

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 30000 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 ß-myosin heavy chain (MHC-ß) 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.


Assuntos
Miosinas Cardíacas/genética , Cardiomiopatia Hipertrófica Familiar/genética , Causas de Morte , Mutação , Miocárdio/patologia , Cadeias Pesadas de Miosina/genética , Adolescente , Substituição de Aminoácidos , Autopsia , Miosinas Cardíacas/metabolismo , Cardiomiopatia Hipertrófica Familiar/metabolismo , Cardiomiopatia Hipertrófica Familiar/patologia , Cardiomiopatia Hipertrófica Familiar/fisiopatologia , DNA/química , DNA/metabolismo , Morte Súbita/etiologia , Exoma , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Miocárdio/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Análise de Sequência de DNA
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