Sudden unexpected death in the young — Value of massive parallel sequencing in postmortem genetic analyses. (December 2018)

• Record Type: Journal Article
• Authors: Scheiper, Stefanie; Ramos-Luis, Eva; Blanco-Verea, Alejandro; Niess, Constanze; Beckmann, Britt-Maria; Schmidt, Ulrike; Kettner, Mattias; Geisen, Christof; Verhoff, Marcel A.; Brion, Maria; Kauferstein, Silke
• Is Part Of: Forensic science international. Volume 293(2018)
• Page Start: 70
• Page End: 76
• Publication Date: 2018-12
• Subjects: Massive parallel sequencing -- Sudden death -- Sudden cardiac death -- Genetics -- Arrhythmia syndromes; Medical jurisprudence -- Periodicals; Chemistry, Forensic -- Periodicals; Forensic Medicine -- Periodicals; Médecine légale -- Périodiques; Chimie légale -- Périodiques; Gerechtelijke geneeskunde; Gerechtelijke chemie; Gerechtelijke psychiatrie; Chemistry, Forensic; Medical jurisprudence; Electronic journals; Periodicals; Electronic journals; 614.1
• DOI: 10.1016/j.forsciint.2018.09.034
• Languages: English
• ISSNs: 0379-0738

Abstract

Highlights: Massive parallel sequencing using a 96-gene panel revealed 9 variants with possibly pathogenic impact in 6 out of 9 sudden unexpected death cases. Sequence variants were mainly detected in other than the major candidate genes associated with sudden cardiac death. Genetic findings in arrhythmia-associated genes represent a potential risk factor for sudden death in epilepsy. Comprehensive background information can be of essential value for variant interpretation and assessment of risk for first-degree relatives. Abstract: Cases of sudden cardiac death (SCD) in young and apparently healthy individuals represent a devastating event in affected families. Hereditary arrhythmia syndromes, which include primary electrical heart disorders as well as cardiomyopathies, are known to contribute to a significant number of these sudden death cases. We performed postmortem genetic analyses in young sudden death cases (aged <45 years) by means of a defined gene panel using massive parallel sequencing (MPS). The data were evaluated bioinformatically and detected sequence variants were assessed using common databases and applying in silico prediction tools. In this study, we identified variants with likely pathogenic effect in 6 of 9 sudden unexpected death (SUD) cases. Due to the detection of numerous unknown and unclassified variants, interpretation of the results proved to be challenging. However, by means of an appropriate evaluation of the findings, MPS represents an important tool to support the forensic investigation and implies great progress for relatives of young SCD victims facilitating adequate risk stratification and genetic counseling.