Whole Genome Sequencing Research Articles

Modification of carbapenemase inhibition test and comparison of its performance with NG-Test CARBA 5 for detection of carbapenemase-producing enterobacterales.

Adequately and accurately identifying carbapenemase-producing Enterobacterales (CPE) is vital for selecting appropriate antimicrobial therapy and implementing effective infection control measures. This study aims to optimize the phenotypic detection method of carbapenemase for routine diagnostics in clinical microbiology laboratories. Carbapenemase genes in 2665 non-duplicate carbapenem-resistant Enterobacterales (CRE) clinical strains collected from various regions of China were confirmed through whole-genome sequencing (WGS). The carbapenemase inhibition test (CIT) was conducted and interpreted using different methods and breakpoints, then compared with the NG-Test CARBA 5 for carbapenemase detection. The diagnostic performance of the CIT method was optimal when the carbapenemase types were determined by comparing the inhibition zone diameters of the imipenem disc with 3-aminophenylboronic acid (APB) plus ethylenediaminetetraacetic acid (EDTA) to those of the imipenem disc with either APB or EDTA alone, with a breakpoint of 4mm. The overall sensitivities of the current CIT, the modified CIT and NG-Test CARBA 5 were 91.4%, 94.9% and 99.9%, respectively. For detecting isolates co-producing Klebsiella pneumoniae carbapenemase (KPC) and metallo-β-lactamases (MBLs), the modified CIT method had higher sensitivity than the current method (70.0%vs. 53.3%), though this difference was not statistically significant (p=0.063). The NG-Test CARBA 5 showed excellent performance for multi-carbapenemases diagnosis, with sensitivity and specificity of 97.1% and 100%, respectively. Optimizing and standardizing the CIT method for clinical use is necessary. It has certain advantages in diagnosing multi-carbapenemase and rare carbapenemase production. However, for identifying common carbapenemase types, the NG-Test CARBA 5 demonstrated superior performance.

Senecavirus cetus a novel picornavirus isolated from cetaceans represents a major host switching to the marine environment

Senecavirus A (SVA), an emerging virus that causes vesicular disease in swine, was, until recently, the only member of the Senecavirus genus (Picornaviridae). Here, we report the isolation and complete genome sequence of two isolates of cetacean picornavirus 1 (Senecavirus cetus), a novel picornavirus species of the Senecavirus genus from dead stranded cetaceans from Alaska. One isolate was from a harbor porpoise stranded in 2017, and another from a beluga whale, stranded in 2019. Whole-genome sequencing of Senecavirus cetus strains showed a genome-wide nucleotide identity of 98.8% and a genome size of 7455 nucleotides. The Senecavirus cetus genomes are most similar to SVA with a 58.3% genome-wide pairwise nucleotide identity. Infection of eleven available cell lines from terrestrial and aquatic animals showed that beluga and sheep cells were susceptible to infection by Senecavirus cetus. Phylogenetic and ancestral state reconstruction analyses supported the novel virus being a member of the Senecavirus genus and provided the first evidence of Senecavirus-like picornavirus infecting marine mammals and likely descending from a terrestrial host ancestor. These discoveries provided important information on the evolutionary relationships and taxonomy of picornaviruses and increased our understanding of the genomic characteristics and potential host range of Senecavirus cetus.

Nosema bombycis: A remarkable unicellular parasite infecting insects.

Microsporidia are opportunistic fungal-like pathogens that cause microsporidiosis, which results in significant economic losses and threatens public health. Infection of domesticated silkworms by the microsporidium Nosema bombycis causes pébrine disease, for which this species of microsporidia has received much attention. Research has been conducted extensively on this microsporidium over the past few decades to better understand its infection, transmission, host-parasite interaction, and detection. Several tools exist to study this species including the complete genome sequence of N. bombycis. In addition to the understanding of N. bombycis being important for the silkworm industry, this species has become a model organism for studying microsporidia. Research on biology of N. bombycis will contribute to the development of knowledge regarding microsporidia and potential antimicrosporidia drugs. Furthermore, this will provide insight into the molecular evolution and functioning of other fungal pathogens.

Diagnostic Yield of Trio Whole-Genome Sequencing in Children with Undiagnosed Developmental Delay or Congenital Anomaly: A Prospective Cohort Study

Diagnostic Yield of Trio Whole-Genome Sequencing in Children with Undiagnosed Developmental Delay or Congenital Anomaly: A Prospective Cohort Study

Association mapping with a diverse population of Puccinia graminis f. sp. tritici identified avirulence loci interacting with the barley Rpg1 stem rust resistance gene

BackgroundWheat stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), is an important disease of barley and wheat. A diverse sexual Pgt population from the Pacific Northwest (PNW) region of the US contains a high proportion of individuals with virulence on the barley stem rust resistance (R) gene, Rpg1. However, the evolutionary mechanisms of this virulence on Rpg1 are mysterious considering that Rpg1 had not been deployed in the region and the gene had remained remarkably durable in the Midwestern US and prairie provinces of Canada.Methods and resultsTo identify AvrRpg1 effectors, genome wide association studies (GWAS) were performed using 113 Pgt isolates collected from the PNW (n = 89 isolates) and Midwest (n = 24 isolates) regions of the US. Disease phenotype data were generated on two barley lines Morex and the Golden Promise transgenic (H228.2c) that carry the Rpg1 gene. Genotype data was generated by whole genome sequencing (WGS) of 96 isolates (PNW = 89 isolates and Midwest = 7 isolates) and RNA sequencing (RNAseq) data from 17 Midwestern isolates. Utilizing ~1.2 million SNPs generated from WGS and phenotype data (n = 96 isolates) on the transgenic line H228.2c, 53 marker trait associations (MTAs) were identified. Utilizing ~140 K common SNPs generated from combined analysis of WGS and RNAseq data, two significant MTAs were identified using the cv Morex phenotyping data. The 55 MTAs defined two distinct avirulence loci, on supercontig 2.30 and supercontig 2.11 of the Pgt reference genome of Pgt isolate CRL 75-36-700-3. The major avirulence locus designated AvrRpg1A was identified with the GWAS using both barley lines and was delimited to a 35 kb interval on supercontig 2.30 containing four candidate genes (PGTG_10878, PGTG_10884, PGTG_10885, and PGTG_10886). The minor avirulence locus designated AvrRpg1B identified with cv Morex contained a single candidate gene (PGTG_05433). AvrRpg1A haplotype analysis provided strong evidence that a dominant avirulence gene underlies the locus.ConclusionsThe association analysis identified strong candidate AvrRpg1 genes. Further analysis to validate the AvrRpg1 genes will fill knowledge gaps in our understanding of rust effector biology and the evolution and mechanism/s of Pgt virulence on Rpg1.

Identification of copy-number variants in patients with overgrowth disorders.

Overgrowth syndromes (OGS) comprise a heterogeneous group of disorders whose main characteristic is that the weight, height or the head circumference are above the 97th centile or 2-3 standard deviations above the mean for age, gender, and ethnic group. Several copy-number variants (CNVs) have been associated with the development of OGS, such as the 5q35 microdeletion or the duplication of the 15q26.1-qter, among many others. In this study, we have applied 850K SNP-arrays to 112 patients and relatives with OGS from the Spanish OverGrowth Registry Initiative. We have identified CNVs associated with the disorder in nine individuals (8%). Subsequently, whole genome sequencing (WGS) analysis was performed in these nine samples in order to better understand these genomic imbalances. All the CNVs were detected by both techniques, settling that WGS is a useful tool for CNV detection. We have found six patients with genomic abnormalities associated with previously well-established disorders and three patients with CNVs of unknown significance, which may be related to OGS, based on scientific literature. In this report, we describe these findings and comment on genes associated with OGS that are located within the CNV regions.

Characteristics and Clinical Value of MYC , BCL2, and BCL6 Rearrangement Detected by Next-generation Sequencing in DLBCL.

MYC , BCL2, and BCL6 rearrangements are clinically important events of diffuse large B-cell lymphoma (DLBCL). The ability and clinical value of targeted next-generation sequencing (NGS) in the detection of these rearrangements in DLBCL have not been fully determined. We performed targeted NGS (481-gene-panel) and break-apart FISH of MYC , BCL2, and BCL6 gene regions in 233 DLBCL cases. We identified 88 rearrangements (16 MYC ; 20 BCL2 ; 52 BCL6 ) using NGS and 96 rearrangements (28 MYC ; 20 BCL2 ; 65 BCL6 ) using FISH. The consistency rates between FISH and targeted NGS for the detection of MYC , BCL2, and BCL6 rearrangements were 93%, 97%, and 89%, respectively. FISH-cryptic rearrangements (NGS+/FISH-) were detected in 7 cases (1 MYC ; 3 BCL2 ; 2 BCL6 ; 1 MYC::BCL6 ), mainly caused by small chromosomal insertions and inversions. NGS-/FISH+ were detected in 38 cases (14 MYC ; 4 BCL2 ; 20 BCL6 ).To clarify the cause of the inconsistencies, we selected 17 from the NGS-/FISH+ rearrangements for further whole genome sequencing (WGS), and all 17 rearrangements were detected with break points by WGS. These break points were all located outside the region covered by the probe of targeted NGS, and most (16/17) were located in the intergenic region. These results indicated that targeted NGS is a powerful clinical diagnostics tool for comprehensive MYC , BCL2, and BCL6 rearrangement detection. Compared to FISH, it has advantages in describing the break point distribution, identifying uncharacterized partners, and detecting FISH-cryptic rearrangements. However, the lack of high-sensitivity caused by insufficient probe coverage is the main limitation of the current technology.

Genotypic and phenotypic characterisation of a nosocomial outbreak of Candida auris in Spain during 5 years.

The investigation of Candida auris outbreaks is needed to provide insights into its population structure and transmission dynamics. We genotypically and phenotypically characterised a C. auris nosocomial outbreak occurred in Consorcio Hospital General Universitario de Valencia (CHGUV), Spain. Data and isolates were collected from CHGUV from September 2017 (first case) until September 2021. Thirty-five isolates, including one from an environmental source, were randomly selected for whole genome sequencing (WGS), and the genomes were analysed along with a database with 335 publicly available genomes, assigning them to one of the five major clades. In order to identify polymorphisms associated with drug resistance, we used the fully susceptible GCA_003014415.1 strain as reference sequence. Known mutations in genes ERG11 and FKS1 conferring resistance to fluconazole and echinocandins, respectively, were investigated. Isolates were classified into aggregating or non-aggregating. All isolates belonged to clade III and were from an outbreak with a single origin. They clustered close to three publicly available genomes from a hospital from where the first patient was transferred, being the probable origin. The mutation VF125AL in the ERG11 gene, conferring resistance to fluconazole, was present in all the isolates and one isolate also carried the mutation S639Y in the FKS1 gene. All the isolates had a non-aggregating phenotype (potentially more virulent). Isolates are genotypically related and phenotypically identical but one with resistance to echinocandins, which seems to indicate that they all belong to an outbreak originated from a single isolate, remaining largely invariable over the years. This result stresses the importance of implementing infection control practices as soon as the first case is detected or when a patient is transferred from a setting with known cases.

Emergence of Bluetongue Virus Serotype 3, the Netherlands, September 2023.

Since 1998, notifiable bluetongue virus (BTV) serotypes 1-4, 6, 8, 9, 11, and 16 have been reported in Europe. In August 2006, a bluetongue (BT) outbreak caused by BTV serotype 8 began in northwestern Europe. The Netherlands was declared BT-free in February 2012, and annual monitoring continued. On September 3, 2023, typical BT clinical manifestations in sheep were notified to the Netherlands Food and Product Safety Consumer Authority. On September 6, we confirmed BTV infection through laboratory diagnosis; notifications of clinical signs in cattle were also reported. We determined the virus was serotype 3 by whole-genome sequencing. Retrospective analysis did not reveal BTV circulation earlier than September. The virus source and introduction route into the Netherlands remains unknown. Continuous monitoring and molecular diagnostic testing of livestock will be needed to determine virus spread, and new prevention strategies will be required to prevent BTV circulation within the Netherlands and Europe.

A multiomic characterization of the leukemia cell line REH using short- and long-read sequencing.

The B-cell acute lymphoblastic leukemia (ALL) cell line REH, with the t(12;21) ETV6::RUNX1 translocation, is known to have a complex karyotype defined by a series of large-scale chromosomal rearrangements. Taken from a 15-yr-old at relapse, the cell line offers a practical model for the study of pediatric B-ALL. In recent years, short- and long-read DNA and RNA sequencing have emerged as a complement to karyotyping techniques in the resolution of structural variants in an oncological context. Here, we explore the integration of long-read PacBio and Oxford Nanopore whole-genome sequencing, IsoSeq RNA sequencing, and short-read Illumina sequencing to create a detailed genomic and transcriptomic characterization of the REH cell line. Whole-genome sequencing clarified the molecular traits of disrupted ALL-associated genes including CDKN2A, PAX5, BTG1, VPREB1, and TBL1XR1, as well as the glucocorticoid receptor NR3C1 Meanwhile, transcriptome sequencing identified seven fusion genes within the genomic breakpoints. Together, our extensive whole-genome investigation makes high-quality open-source data available to the leukemia genomics community.

Phylogeographic Analysis of Mycobacterium kansasii Isolates from Patients with M. kansasii Lung Disease in Industrialized City, Taiwan.

Little is known about environmental transmission of Mycobacterium kansasii. We retrospectively investigated potential environmental acquisition, primarily water sources, of M. kansasii among 216 patients with pulmonary disease from an industrial city in Taiwan during 2015-2017. We analyzed sputum mycobacterial cultures using whole-genome sequencing and used hierarchical Bayesian spatial network methods to evaluate risk factors for genetic relatedness of M. kansasii strains. The mean age of participants was 67 years; 24.1% had previously had tuberculosis. We found that persons from districts served by 2 water purification plants were at higher risk of being infected with genetically related M. kansasii isolates. The adjusted odds ratios were 1.81 (1.25-2.60) for the Weng Park plant and 1.39 (1.12-1.71) for the Fongshan plant. Those findings unveiled the association between water purification plants and M. kansasii pulmonary disease, highlighting the need for further environmental investigations to evaluate the risk for M. kansasii transmission.

Identification and genomic analyses of a Streptococcus suis ST25 strain associated with the first human septicemia in mainland China

Streptococcus suis (S. suis) is a Gram-positive bacterium and the main culprit behind zoonotic outbreaks, posing a serious threat to public health. The prevalent strains in China are mainly of sequence types (ST) 1 and 7, with few cases of human infections caused by other sequence type being reported. This study presents the first isolation of a ST25 strain from the blood of a septicemic patient. A 57-year-old febrile patient was admitted to a hospital in Hainan of China, diagnosed as septicemia and hepatic dysfunction. A strain of S. suis was isolated from blood culture and confirmed to be serotype 2 and ST25 through 16S rRNA sequencing and whole-genome sequencing, and its genome was further analyzed for gene functions and presence of drug resistance genes. The full-length genome of strain HN28 spans 2,280,124 bp and encodes a total of 2291 proteins. Genes annotated in COG, GO, KEGG, CAZy, and PHl databases accounted for 75.38 %, 69.14 %, 55.35 %, 4.58 %, and 11.87 % of the total predicted proteins, respectively. Virulence factor analysis revealed the presence of seven putative virulence genes in strain HN28. Analysis using the CARD database identified 51 resistance genes in HN28, alongside abundant exocytosis systems. These findings underscore the occurrence of S. suis infections in humans caused by less common ST, emphasizing the need for enhanced epidemiological investigations and monitoring of S. suis infections in the human population.

Whole-genome sequencing of Western Canadian Borrelia spp. collected from diverse tick and animal hosts reveals short-lived local genotypes interspersed with longer-lived continental genotypes.

Changing climates are allowing the geographic expansion of ticks and their animal hosts, increasing the risk of Borrelia-caused zoonoses in Canada. However, little is known about the genomic diversity of Borrelia from the west of the Canadian Rockies and from the tick vectors Ixodes pacificus, Ixodes auritulus and Ixodes angustus. Here, we report the whole-genome shotgun sequences of 51 Borrelia isolates from multiple tick species collected on a range of animal hosts between 1993 and 2016, located primarily in coastal British Columbia. The bacterial isolates represented three different species from the Lyme disease-causing Borrelia burgdorferi sensu lato genospecies complex [Borrelia burgdorferi sensu stricto (n=47), Borrelia americana (n=3) and Borrelia bissettiae (n=1)]. The traditional eight-gene multi-locus sequence typing (MLST) strategy was applied to facilitate comparisons across studies. This identified 13 known Borrelia sequence types (STs), established 6 new STs, and assigned 5 novel types to the nearest sequence types. B. burgdorferi s. s. isolates were further differentiated into ten ospC types, plus one novel ospC with less than 92 % nucleotide identity to all previously defined ospC types. The MLST types resampled over extended time periods belonged to previously described STs that are distributed across North America. The most geographically widespread ST, ST.12, was isolated from all three tick species. Conversely, new B. burgdorferi s. s. STs from Vancouver Island and the Vancouver region were only detected for short periods, revealing a surprising transience in space, time and host tick species, possibly due to displacement by longer-lived genotypes that expanded across North America.This article contains data hosted by Microreact.

Characteristics and comparative genome analysis of Yersinia enterocolitica and related species associated with human infections in Switzerland 2019–2023

PurposeWe aimed to characterise Yersinia enterocolitica from human clinical specimens in Switzerland using epidemiological, microbiological and whole-genome sequencing (WGS) data. MethodsIsolates (n = 149) were collected between January 2019 and December 2023. Epidemiological data was noted and strains were characterized by biochemical and serological typing, antimicrobial susceptibility testing (AST), and WGS-based analysis. ResultsMost of the isolates (86%) were from stool specimens and 52% were from male patients. The patients' median age was 28 years (< 1–94 years). Typing assigned the isolates to bioserotype 4/O:3 (44%), biotype 1 A (34%), bioserotype 2/O:9 (21%), and bioserotype 3/O:3 (1%). WGS identified Y. enterocolitica (n = 147), Y. alsatica (n = 1) and Y. proxima (n = 1). Seven isolates were multidrug resistant (MDR) and harboured plasmid pAB829 carrying aph(3″)-Ib, aph(6)-Id, and tet(Y) (n = 1), pAC120 carrying aph(6)-Id and tet(A) (n = 2), or a 12.6 kb Tn2670-like transposon containing catA1, aadA12, sul1, and qacEΔ1 (n = 4). Virulence factors (VFs) included ail (n = 99), invB, (n = 145), ystA (n = 99), ystB (n = 48) and pYV-associated VFs (n = 93). MLST and cgMLST analysis showed that BT 1 A strains consisted of several STs and were highly diverse, whereas BT 2/O:9 strains were all ST12 and clustered closely, and BT4/O:3 strains mostly belonged to ST18 but were more diverse. SNP analysis revealed two highly clonal BT4/O:3 subpopulations with wide spatio-temporal distribution. ConclusionsY. enterocolitica BT1A, BT 2/O:9 and BT4/O:3 are frequently associated with human yersiniosis in Switzerland. WGS-based subtyping of Y. enterocolitica is a powerful tool to explore the genetic diversity and the pathogenic potential of human isolates.

Southern African Origin of HTLV-1 in Romania.

In Europe, most HTLV-1-infected individuals originate from highly endemic regions such as West Indies, sub-Saharan Africa, and South America. The only genuine endemic region for HTLV-1 in Europe is Romania where ATL series have been reported among Romanian patients. Our objective is to better understand the origin of this endemic focus based on a study of the genetic diversity of HTLV-1 in Romanians. DNA was obtained from PBMCs/buffy coats of 11 unrelated HTLV-1-infected individuals of Romanian origin. They include 9 ATL cases and 2 asymptomatic carriers. LTR sequences were obtained for all specimens. Complete genomic HTLV-1 sequences were obtained using four PCR series on 10 specimens. Phylogenetic trees were generated from multiple alignments using HTLV-1 prototypic sequences and the new generated sequences. Most of the complete LTR sequences (756-bp) showed low nucleotide diversity, ranging from 0% to 0.8% difference, and were closely related (less than 0.8% divergence) to the only previously characterized Romanian strain, RKI2. One strain, ROU7, diverged slightly (1.5% on average) from the others. Phylogenetic analyses both on partial LTR and the complete genome demonstrate that the 11 sequences belong to the HTLV-1a cosmopolitan genotype and 10 of them belong to the previously denominated a-TC Mozambique-Southern Africa A subgroup. In this study, we demonstrated that the HTLV-1 present in Romania most probably originated in Southern Africa. As most Romanian HTLV-1 strains are very closely related, we can assume that HTLV-1 has been introduced into the Romanian population recently. Further studies are ongoing to decipher the routes of arrival and dissemination of these HTLV-1 strains, and to date the emergence of this endemic focus in Central Europe.

Detection of lumpy skin disease virus reads in the human upper respiratory tract microbiome requires further investigation.

Lumpy skin disease virus (LSDV), a double-stranded DNA virus from the Capripoxvirus genus, primarily affects Bos indicus, Bos taurus breeds, and water buffalo. Arthropod vectors, including mosquitoes and biting flies, are the main LSDV transmitters. Although LSDV is not zoonotic, this study unexpectedly detected LSDV reads in the upper respiratory tract microbiome of humans from rural and urban areas in Maharashtra, India. Nasopharyngeal and oropharyngeal swab samples collected for SARS-CoV-2 surveillance underwent whole-genome metagenomics sequencing, revealing LSDV reads in 25% of samples. Split kmer analysis provided insights into sample relatedness despite the low coverage of LSDV reads with the reference genome. Our findings, which include the detection of LSDV contigs aligning to specific locations on the reference genome, suggest a common source for LSDV reads, potentially shared water sources, or milk/milk products. Further investigation is needed to ascertain the mode of transmission and reason for the detection of LSDV reads in human upper respiratory tract.

Methylation of EjNAC5 and its interactions with other transcription factors regulate loquat fruit chilling lignification.

Changes in both lignin biosynthesis and DNA methylation have been reported to be associated with chilling stress in plants. When stored at low temperatures, red-fleshed loquat is prone to lignification, with increased lignin content and fruit firmness, which has deleterious effects on taste and eating quality. Here, we found that 5°C storage mitigated the increasing firmness and lignin content of red-fleshed 'Dahongpao' ('DHP') loquat fruit that occurred during 0°C storage. EjNAC5 was identified by integrating RNA sequencing with whole-genome bisulfite sequencing analysis of 'DHP' loquat fruit. The transcript levels of EjNAC5 were positively correlated with changes in firmness and negatively correlated with changes in DNA methylation level of a differentially methylated region (DMR) in the EjNAC5 promoter. In white-fleshed 'Baisha' ('BS') loquat fruit, which do not undergo chilling-induced lignification at 0°C, the transcripts of EjNAC5 remained low and the methylation levels of the DMR in the EjNAC5 promoter was higher, compared to 'DHP' loquat fruit. Transient overexpression of EjNAC5 in loquat fruit and stable overexpression in Arabidopsis and liverwort led to an increase in lignin content. Furthermore, EjNAC5 interacts with EjERF39 and EjHB1 and activates the transcription of Ej4CL1 and EjPRX12 genes involved in lignin biosynthesis. This regulatory network involves different TFs to those involved in lignification pathway. Our study indicates that EjNAC5 promoter methylation modulates EjNAC5 transcript levels and identifies novel EjNAC5-EjERF39-Ej4CL1 and EjNAC5-EjHB1-EjPRX12 regulatory modules involved in chilling induced-lignification.

Complete genome sequence of Erwinia pyrifoliae strain YKB12327, isolated from an apple tree in Korea

Complete genome sequence of Erwinia pyrifoliae strain YKB12327, isolated from an apple tree in Korea

Phylogenetic analysis and molecular genetic characteristics of West Nile virus lineage 2 isolates circulating in the Russian Federation.

Since its initial detection in Africa, the West Nile virus has disseminated widely across all continents, becoming endemic in numerous countries, including the Russian Federation. A substantial expansion of the West Nile virus range was observed in the European part of the Russian territory in 1999. In light of this epidemiological trend, research endeavours focusing on monitoring West Nile virus circulation activity in endemic regions of the country have gained paramount significance. A substantial dataset has been accrued from 2007 onwards regarding genomic variability and dissemination dynamics across the country throughout the entire monitoring period for the West Nile fever pathogen. The objective of this study was to characterise West Nile virus isolates that have been circulating in the Russian Federation and identify their molecular and genetic characteristics. A phylogenetic analysis of 55 complete genome sequences revealed that the West Nile virus population within the Russian Federation is genetically heterogeneous and is represented by four major clades. One of these clades is currently exhibiting extensive spread into new regions of the country.

Novel variants in TECRL leading to catecholaminergic polymorphic ventricular tachycardia.

Pathogenic and likely pathogenic variants in the TECRL gene are known to be associated with recessive catecholaminergic polymorphic ventricular tachycardia 3, which can include prolonged QT intervals (MIM#614021). We report a case of cardiac arrest in a previously healthy adolescent male in the community. The patient was found to have a novel maternally inherited likely pathogenic variant in TECRL (c.915T>G [p.Tyr305Ter]) and an additional 19-kb duplication encompassing multiple exons of TECRL (chr4:65165944-65185287, dup [4q13.1]) not identified in the mother. Genetic results were revealed via rapid whole-genome sequencing, which allowed appropriate treatment and prognostication.