Molecular investigation by whole exome sequencing revealed a high proportion of pathogenic variants among Thai victims of sudden unexpected death syndrome

作者：Suktitipat Bhoom; Sathirareuangchai Sakda; Roothumnong Ekkapong; Thongnoppakhun Wanna; Wangkiratikant Purin; Vorasan Nutchavadee; Krittayaphong Rungroj; Pithukpakorn Manop; Boonyapisit Warangkna

来源：PLos One, 2017, 12(7): e0180056.

DOI：10.1371/journal.pone.0180056

Introduction Sudden unexpected death syndrome (SUDS) is an important cause of death in young healthy adults with a high incident rate in Southeast Asia; however, there are no molecular autopsy reports about these victims. We performed a combination of both a detailed autopsy and a molecular autopsy by whole exome sequencing (WES) to investigate the cause of SUDS in Thai sudden death victims.
Materials and methods A detailed forensic autopsy was performed to identify the cause of death, followed by a molecular autopsy, in 42 sudden death victims who died between January 2015 and August 2015. The coding sequences of 98 SUDS-related genes were sequenced using WES. Potentially causative variants were filtered based on the variant functions annotated in the dbNSFP database. Variants with inconclusive clinical significance evidence in ClinVar were resolved with a variant prediction algorithm, metaSVM, and the frequency data of the variants found in public databases, such as the 1000 Genome Project, ESP6500 project, and the Exome Aggregation Consortium (ExAc) project.
Results Combining both autopsy and molecular autopsy enabled the potential identification of cause of death in 81% of the cases. Among the 25 victims with WES data, 72% (18/25) were found to have potentially causative SUDS mutations. The majority of the victims had at a mutation in the TTN gene (8/18 = 44%), and only one victim had an SCN5A mutation.
Conclusions WES can help to identify the genetic causes in victims of SUDS and may help to further guide investigations into their relatives to prevent additional SUDS victims.

• 出版日期2017-7-13