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

Date Published: July 13, 2017

Publisher: Public Library of Science

Author(s): Bhoom Suktitipat, Sakda Sathirareuangchai, Ekkapong Roothumnong, Wanna Thongnoppakhun, Purin Wangkiratikant, Nutchavadee Vorasan, Rungroj Krittayaphong, Manop Pithukpakorn, Warangkna Boonyapisit, Chunhua Song.

http://doi.org/10.1371/journal.pone.0180056

Abstract

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.

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.

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.

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.

Partial Text

Sudden death is one of the common causes of death worldwide. These tragic events can cause medico-legal issues among families and society. It is of great importance to establish the cause of death because of the potential for screening and prophylactic treatment among family members. However, screening autopsy-negative cases, including normal heart and normal toxicology, could be diagnostically challenging. Many of these unexpected deaths can be attributed to lethal arrhythmia disorders, such as hereditary cardiac arrhythmias [1].

A significant proportion of Thai victims with SUDS is caused by various inherited genetic abnormalities, especially in young individuals with no abnormal structural heart diseases by autopsy. Genetic investigation by NGS provides an affordable and powerful diagnostic tool in SUDS and could prevent further loss through family screening and lifesaving management among victims’ family members.

 

Source:

http://doi.org/10.1371/journal.pone.0180056

 

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