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

@entity1788 @entity943 @entity944 @entity146 @entity9678 @entity23963 @entity299 @entity13192 @entity796 @entity204 @entity65 @entity46789
UNASSIGNED: Genetic testing for cardiac @entity13192 in @entity944 ( @entity944 ) has developed substantially over the last years. The Next Generation Sequencing (NGS) technology provides an unprecedented opportunity to screen for genetic variations underlying arrhythmogenic genes in a short period of time at a low cost. The present study aimed to perform genetic testing with NGS technologies on the Ion Torrent Personal Genome Machine    (Ion @entity46789   ) sequencer, in targeting a total of 23 genes reported to be associated with @entity299 in order to identify the possible cause of @entity204 in a cohort of post-mortem cases. The molecular analyses focused on 16 cases of @entity944 , aged less than 35 years old. In all cases, the cause of @entity204 could not be determined after a rigorous autopsy associated with histopathological and toxicological analyses according to the guidelines of the Association for European @entity65 . DNA was extracted from fresh frozen tissue. An average of 200 variants was identified per case. However, after the prioritization process using a new scoring program (VaRank) and after the conjunction of clinical data and molecular findings, four "likely pathogenic" variants (including two undescribed variants), were identified in three cases (18.75%) of our cohort in the genes @entity9678 , @entity796 , @entity1788 and @entity23963 . One case, who died during @entity146 hospitalization after administration of a QT prolonging drug, showed a double "likely pathogenic" variant in Long QT genes ( @entity796 and @entity1788 ) which may have predisposed to drug-induced @entity943 . Our study illustrates that the NGS approach based on AmpliSeq    libraries and Ion Torrent PGM    sequencing may be an efficient approach, integrated to post-mortem examination. Given the massive amount of information generated by NGS, a rigorous filtration strategy of variants coupled with multidisciplinary collaboration is crucial to determine the potential pathogenic role of identified variants in the cause of @entity204 .
