Genotype and clinical characteristics of congenital long QT syndrome in Thailand.

Congenital long QT syndrome (LQTS) is an inheritable arrhythmic disorder which is linked to at least 17 genes. The clinical characteristics and genetic mutations may be variable among different population groups and they have not yet been studied in Thai population. Clinical characteristics were retrospectively reviewed from children and young adults with congenital long QT syndrome whose blood samples were sent for genotyping during 1998-2017. Sangers sequencing was used to sequentially identify KCNQ1 or KCNH2 genetic variants. Whole exome sequencing (WES) was used to identify variants in all other known LQTS genes. Of the 20 subjects (17 families), 45% were male, mean QTc was 550.3 ± 68.8 msec (range 470-731 msec) and total Schwartz's score was 5.6 ± 1.2 points (range 3-8 points). Fifty percent of patients had events at rest, 30% had symptoms after adrenergic mediated events, and 20% were asymptomatic. We discovered pathogenic and likely pathogenic genetic variants in KCNQ1, KCNH2, and SCN5A in 6 (35%), 4 (24%), and 2 (12%) families, respectively. One additional patient had variance of unknown significance (VUS) in KCNH2 and another one in ANK2. No pathogenic genetic variant was found in 3 patients (18%). Most patients received beta-blocker and 9 (45%) had ICD implanted. LQT1 patients were either asymptomatic or had stress-induced arrhythmia. Most of the LQT2 and LQT3 patients developed symptoms at rest or during sleep. Our patients with LQTS were mostly symptomatic at presentation. The genetic mutations were predominantly in LQT1, LQT2, and LQT3 genes

High prevalence of circulating DS-1-like human rotavirus A and genotype diversity in children with acute gastroenteritis in Thailand from 2016 to 2019

Background: Human rotavirus A (RVA) infection is the primary cause of acute gastroenteritis (AGE) in infants and young children worldwide, especially in children under 5 years of age and is a major public health problem causing severe diarrhea in children in Thailand. This study aimed to investigate the prevalence, genotype diversity, and molecular characterization of rotavirus infection circulating in children under 15 years of age diagnosed with AGE in Thailand from January 2016 to December 2019. Methods: A total of 2,001 stool samples were collected from children with gastroenteritis (neonates to children <15 years of age) and tested for RVA by real-time polymerase chain reaction (RT-PCR). Amplified products were sequenced and submitted to an online genotyping tool for analysis. Results: Overall, 301 (15.0) stool samples were positive for RVA. RVA occurred most frequently among children aged 0-24 months. The seasonal incidence of rotavirus infection occurred typically in Thailand during the winter months (December-March). The G3P8 genotype was identified as the most prevalent genotype (33.2%, 100/301), followed by G8P8 (10.6%, 32/301), G9P8 (6.3%, 19/301), G2P4 (6.0%, 18/301), and G1P6 (5.3%, 16/301). Uncommon G and P combinations such as G9P4, G2P8, G3P4 and G3P9 were also detected at low frequencies. In terms of genetic backbone, the unusual DS-1-like G3P8 was the most frequently detected (28.2%, 85/301), and the phylogenetic analysis demonstrated high nucleotide identity with unusual DS-1-like G3P8 detected in Thailand and several countries. Conclusions: A genetic association between RVA isolates from Thailand and other countries ought to be investigated given the local and global dissemination of rotavirus as it is crucial for controlling viral gastroenteritis, and implications for the national vaccination programs. © 2021 Pasittungkul et al

Common and rare susceptibility genetic variants predisposing to Brugada syndrome in Thailand.

BACKGROUND Mutations in SCN5A are rarely found in Thai patients with Brugada syndrome (BrS). Recent evidence suggested that common genetic variations may underlie BrS in a complex inheritance model.OBJECTIVE The purpose of this study was to find common and rare/low-frequency genetic variants predisposing to BrS in persons in Thailand.METHODS We conducted a genome-wide association study (GWAS) to explore the association of common variants in 154 Thai BrS cases and 432 controls. We sequenced SCN5A in 131 cases and 205 controls. Variants were classified according to current guidelines, and case-control association testing was performed for rare and low frequency variants.RESULTS Two loci were significantly associated with BrS. The first was near SCN5A/SCN10A (lead marker rs10428132; odds ratio [OR] 2.4; P = 3 x 10(-10)). Conditional analysis identified a novel independent signal in the same locus (rs6767797; OR 2.3; P = 2.7 x 10(-10)).The second locus was near HEY2 (lead marker rs3734634; OR 2.5; P = 7 x 10(-) (9)). Rare (minor allele frequency [MAF] &lt;0.0001) coding variants in SCN5A were found in 8 of the 131 cases (6.1% in cases vs 2.0% in controls; P = .046; OR 3.3; 95% confident interval [CI] 1.0-11.1), but an enrichment of low-frequency (MAF 0.001 and 0.0001) variants also was observed in cases, with 1 variant (SCN5A: p.Arg965Cys) detected in 4.6% of Thai BrS patients vs 0.5% in controls (P = 0.015; OR 9.8; 95% CI 1.2-82.3).CONCLUSION The genetic basis of BrS in Thailand includes a wide spectrum of variant frequencies and effect sizes. As previously shown in European and Japanese populations, common variants near SCN5A and HEY2 are associated with BrS in the Thai population, confirming the transethnic transferability of these 2 major BrS loci

Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia

International audienceHuman enterovirus 71 (EV-A71) causes hand, foot and mouth disease (HFMD). EV-A71 circulates in many countries and has caused large epidemics, especially in the Asia-Pacific region, since 1997. In April 2012, an undiagnosed fatal disease with neurological involvement and respiratory distress occurred in young children admitted to the Kantha Bopha Children's Hospital in Phnom Penh, Cambodia. Most died within a day of hospital admission, causing public panic and international concern. In this study, we describe the enterovirus (EV) genotypes that were isolated during the outbreak in 2012 and the following year. From June 2012 to November 2013, 312 specimens were collected from hospitalized and ambulatory patients and tested by generic EV and specific EV-A71 reverse transcription PCR. EV-A71 was detected in 208 clinical specimens while other EVs were found in 32 patients. The VP1 gene and/or the complete genome were generated. Our phylogenetic sequencing analysis demonstrated that 80 EV-A71 strains belonged to the C4a subgenotype and 3 EV-A71 strains belonged to the B5 genotype. Furthermore, some lineages of EV-A71 were found to have appeared in Cambodia following separate introductions from neighboring countries. Nineteen EV A (CV-A6 and CV-A16), 9 EV B (EV-B83, CV-B3, CV-B2, CV-A9, E-31, E-2 and EV-B80) and 4 EV C (EV-C116, EV-C96, CV-A20 and Vaccine-related PV-3) strains were also detected. We found no molecular markers of disease severity. We report here that EV-A71 genotype C4 was the main etiological agent of a large outbreak of HFMD and particularly of severe forms associated with central nervous system infections. The role played by other EVs in the epidemic could not be clearly established