Using whole exome sequencing and bioformatics in the molecular autopsy of a sudden unexplained death syndrome (SUDS)...

Whole exome sequencing (WES) and bioinformatics analysis were used to investigate potential disease-causing gene mutations in a sudden unexplained death syndrome (SUDS) case after autopsy and pathology tests failed to suggest an obvious disease mechanism. Following whole exome sequencing, a 3-step bioinformatics filtering procedure was carried out to identify possible pathogenic genomic features. Single nucleotide variations (SNVs) were analyzed and ranked by likely mutation impact using various open online tools. After screening, we identified G643S as a putative causative heterozygous mutation in the KCNQ1 gene. This mutation has been reported in abnormalities consistent with SUDS, such as IKs in cardiac myocytes, a condition that predisposes for arrhythmias. Our work demonstrates the application of sequencing technology at the whole exome level for determining potential causes of an otherwise unexplained death.