Targeted next generation sequencing application in cardiac channelopathies: Analysis of a cohort of autopsy-negative sudden unexplained deaths

摘要: Abstract Genetic testing for cardiac channelopathies in sudden unexplained death (SUD) has developed substantially over the last years. The Next Generation Sequencing (NGS) technology provides an unprecedented opportunity to screen genetic variations underlying arrhythmogenic genes a short period of time at low cost. present study aimed perform with NGS technologies on Ion Torrent Personal Genome Machine™ (Ion PGM™) sequencer, targeting total 23 reported be associated inherited order identify possible cause cohort post-mortem cases. molecular analyses focused 16 cases SUD, aged less than 35 years old. In all cases, could not determined after rigorous autopsy histopathological and toxicological according guidelines Association European Cardiovascular Pathology. DNA was extracted from fresh frozen tissue. An average 200 variants identified per case. However, prioritization process using new scoring program (VaRank) conjunction clinical data findings, four “likely pathogenic” (including two undescribed variants), were three (18.75%) our KCNH2 , ANK2 SCN5A RYR2 . One case, who died during psychiatric hospitalization administration QT prolonging drug, showed double variant Long ( ) which may have predisposed drug-induced arrhythmias. Our illustrates that approach based AmpliSeq™ libraries PGM™ sequencing efficient approach, integrated examination. Given massive amount information generated by NGS, filtration strategy coupled multidisciplinary collaboration is crucial determine potential pathogenic role death.