SCN5A gene exome sequencing profile in sudden unexplained nocturnal death syndrome in Thai population

Abstract

Background: Sudden unexplained nocturnal death syndrome (SUNDS) or Lai-tai is a sudden death that often
occurs in Southeast Asia. The characteristics of SUNDS cases are healthy young males, 20 – 49 yrs., that suddenly die during sleep with no relevant medical history. Previous studies found that SUNDS is similar to Brugada syndrome (BrS) which correlates to SCN5A mutations. Moreover, SCN5A variations affect sodium ion channel functions are different from one populations to anothers.

Objective: The aim of this study is to describe the phenotype of SUNDS cases in the Thai population and establish SCN5A gene exome sequencing profiles using Next-Generation sequencing.

Methods: All characteristics data of 12 SUNDS cases in the Thai population were collected. Microscopic
examinations were analyzed. Postmortem genetic testing of SCN5A gene exome sequencing profiles in 12 SUNDS cases using Next-Generation Sequencing were performed. Pathogenicities were predicted using Polyphen-2 for missense variants and Mutationtaster for frameshift mutations. As for combined pathogenicity results, Combined Annotation Dependent Depletion (CADD) scores < 20 were filtered out. After that, SCN5A variants were compared with ExAC, 1000G, ClinVar and previous reports. Descriptive analysis in SUNDS cases characteristics were analyzed using Microsoft Excel 2013.

Results: Characteristics of SUNDS cases with microscopic examination in the Thai population were shown. SCN5A gene exome sequencing profile in 12 SUNDS cases in the Thai population were generated. Two frameshift and six missense variants on the SCN5A gene from four SUNDS cases (33.34%) were found that potentially significantly affect sodium channel function. Only G599R has been previously reported. Other variants are novel (T92N, E171G, A178T, L1646fs, N1659S, E1804fs and E2013K).

Conclusion: Phenotype and SCN5A gene exome sequencing profiles for SUNDS cases in the Thai population
were shown. Our results could be useful for forensic pathologists and medical practitioners to keep these variants as a possible risk variants and closely observed in every SUNDS in the Thai population.