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

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.

[Molecular Genetic Analysis of One Sudden Unexplained Death in the Young by Whole Exome Sequencing].

OBJECTIVE: To find the mutation of disease-causing genes of sudden unexplained death syndrome (SUDS) in the young by whole exome sequencing in one case. METHODS: One SUDS case was found no obvious fatal pathological changes after conventional autopsy and pathological examination. The whole exome sequencing was performed with the Ion Torrent PGM™ System with hg19 as reference sequence for sequencing data. The functions of mutations were analyzed by PhyloP, PolyPhen2 and SIFT. A three-step bioinformatics filtering procedure was carried out to identify possible significative single nucleotide variation (SNV), which was missense mutation with allele frequency < 1% of myocardial cell. RESULTS: Four rare suspicious pathogenic SNV were identified. Combined with the analysis of conventional autopsy and pathological examination, the mutation MYOM2 (8_2054058_G/A) was assessed as high-risk deleterious mutation by PolyPhen2 and SIFT, respectively. CONCLUSION: Based on the second generation sequencing technology, analysis of whole exome sequencing can be a new method for the death cause investigation of SUDS. The gene MYOM2 is a new candidate SUDS pathogenic gene for mechanism research.