Background: Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy that mainly affects skeletal muscle. FSHD1 accounts for 95% of all FSHD cases and can be diagnosed based on the pathogenic contraction of the D4Z4-repeat array on chromosome 4q35. Genetic diagnosis of FSHD1 is challenging because of the large size and repetitive nature of the D4Z4 region. We evaluated the clinical applicability of optical genome mapping (OGM) for the genetic diagnosis of FSHD1. Methods: We included 25 individuals with clinically confirmed or suspected/probable FSHD and their families. Ultra-high-molecular-weight DNA from peripheral blood was labeled, stained, and imaged using a single-molecule OGM platform (Bionano Genomics Saphyr system). D4Z4 repeat size and haplotype information were analyzed using the manufacturer’s dedicated pipeline. We also compared the workflow and test time between Southern blot analysis and OGM. Results: We obtained concordant OGM and Southern blot results with 10 samples from patients with clinically confirmed FSHD. The D4Z4 repeat size differed within 1 unit between the Southern blot analysis and OGM. Among nine patients with clinically suspected or probable FSHD, six patients were confirmed to have pathogenic contractions by OGM.In our cohort, one de novo mosaic FSHD1 patient was successfully diagnosed with OGM.Moreover, OGM has a more straightforward and less time-consuming workflow than Southern blot analysis. Conclusions OGM enables accurate and reliable detection of pathogenic contraction of the D4Z4-repeat array and is a valuable tool for the genetic diagnosis of FSHD1.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy that mainly affects skeletal muscle. FSHD1 accounts for 95% of all FSHD cases and can be diagnosed based on the pathogenic contraction of the D4Z4-repeat array on chromosome 4q35. Genetic diagnosis of FSHD1 is challenging because of the large size and repetitive nature of the D4Z4 region. We evaluated the clinical applicability of optical genome mapping (OGM) for the genetic diagnosis of FSHD1. Methods: We included 25 individuals with clinically confirmed or suspected/probable FSHD and their families. Ultra-high-molecular-weight DNA from peripheral blood was labeled, stained, and imaged using a single-molecule OGM platform (Bionano Genomics Saphyr system). D4Z4 repeat size and haplotype information were analyzed using the manufacturer’s dedicated pipeline. We also compared the workflow and test time between Southern blot analysis and OGM. Results: We obtained concordant OGM and Southern blot results with 10 samples from patients with clinically confirmed FSHD. The D4Z4 repeat size differed within 1 unit between the Southern blot analysis and OGM. Among nine patients with clinically suspected or probable FSHD, six patients were confirmed to have pathogenic contractions by OGM.In our cohort, one de novo mosaic FSHD1 patient was successfully diagnosed with OGM.Moreover, OGM has a more straightforward and less time-consuming workflow than Southern blot analysis. Conclusions OGM enables accurate and reliable detection of pathogenic contraction of the D4Z4-repeat array and is a valuable tool for the genetic diagnosis of FSHD1.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy that mainly affects skeletal muscle. FSHD1 accounts for 95% of all FSHD cases and can be diagnosed based on the pathogenic contraction of the D4Z4-repeat array on chromosome 4q35. Genetic diagnosis of FSHD1 is challenging because of the large size and repetitive nature of the D4Z4 region. We evaluated the clinical applicability of optical genome mapping (OGM) for the genetic diagnosis of FSHD1. Methods: We included 25 individuals with clinically confirmed or suspected/probable FSHD and their families. Ultra-high-molecular-weight DNA from peripheral blood was labeled, stained, and imaged using a single-molecule OGM platform (Bionano Genomics Saphyr system). D4Z4 repeat size and haplotype information were analyzed using the manufacturer’s dedicated pipeline. We also compared the workflow and test time between Southern blot analysis and OGM. Results: We obtained concordant OGM and Southern blot results with 10 samples from patients with clinically confirmed FSHD. The D4Z4 repeat size differed within 1 unit between the Southern blot analysis and OGM. Among nine patients with clinically suspected or probable FSHD, six patients were confirmed to have pathogenic contractions by OGM.In our cohort, one de novo mosaic FSHD1 patient was successfully diagnosed with OGM.Moreover, OGM has a more straightforward and less time-consuming workflow than Southern blot analysis. Conclusions OGM enables accurate and reliable detection of pathogenic contraction of the D4Z4-repeat array and is a valuable tool for the genetic diagnosis of FSHD1.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy that mainly affects skeletal muscle. FSHD1 accounts for 95% of all FSHD cases and can be diagnosed based on the pathogenic contraction of the D4Z4-repeat array on chromosome 4q35. Genetic diagnosis of FSHD1 is challenging because of the large size and repetitive nature of the D4Z4 region. We evaluated the clinical applicability of optical genome mapping (OGM) for the genetic diagnosis of FSHD1. Methods: We included 25 individuals with clinically confirmed or suspected/probable FSHD and their families. Ultra-high-molecular-weight DNA from peripheral blood was labeled, stained, and imaged using a single-molecule OGM platform (Bionano Genomics Saphyr system). D4Z4 repeat size and haplotype information were analyzed using the manufacturer’s dedicated pipeline. We also compared the workflow and test time between Southern blot analysis and OGM. Results: We obtained concordant OGM and Southern blot results with 10 samples from patients with clinically confirmed FSHD. The D4Z4 repeat size differed within 1 unit between the Southern blot analysis and OGM. Among nine patients with clinically suspected or probable FSHD, six patients were confirmed to have pathogenic contractions by OGM.In our cohort, one de novo mosaic FSHD1 patient was successfully diagnosed with OGM.Moreover, OGM has a more straightforward and less time-consuming workflow than Southern blot analysis. Conclusions OGM enables accurate and reliable detection of pathogenic contraction of the D4Z4-repeat array and is a valuable tool for the genetic diagnosis of FSHD1.

Background: Structural variants (SVs) are currently analyzed using a combination of conventional methods; however, this approach has limitations. Optical genome mapping (OGM), an emerging technology for detecting SVs using a single-molecule strategy, has the potential to replace conventional methods. We compared OGM with conventional diagnostic methods for detecting SVs in various hematologic malignancies. Methods: Residual bone marrow aspirates from 27 patients with hematologic malignancies in whom SVs were observed using conventional methods (chromosomal banding analysis, FISH, an RNA fusion panel, and reverse transcription PCR) were analyzed using OGM. The concordance between the OGM and conventional method results was evaluated. Results: OGM showed concordance in 63% (17/27) and partial concordance in 37% (10/27) of samples. OGM detected 76% (52/68) of the total SVs correctly (concordance rate for each type of SVs: aneuploidies, 83% [15/18]; balanced translocation, 80% [12/15] unbalanced translocation, 54% [7/13] deletions, 81% [13/16]; duplications, 100% [2/2] inversion 100% [1/1]; insertion, 100% [1/1]; marker chromosome, 0% [0/1];isochromosome, 100% [1/1]). Sixteen discordant results were attributed to the involvement of centromeric/telomeric regions, detection sensitivity, and a low mapping rate and coverage. OGM identified additional SVs, including submicroscopic SVs and novel fusions, in five cases. Conclusions OGM shows a high level of concordance with conventional diagnostic methods for the detection of SVs and can identify novel variants, suggesting its potential utility in enabling more comprehensive SV analysis in routine diagnostics of hematologic malignancies, although further studies and improvements are required.

Background: The mechanism and medical treatment target for degenerative aortic valve disease, including aortic stenosis, is not well studied. In this study, we investigated the effect of clonal hematopoiesis of indeterminate potential (CHIP) on the development of aortic valve sclerosis (AVS), a calcified aortic valve without significant stenosis. Methods: Participants with AVS (valves ≥ 2 mm thick, high echogenicity, and a peak trans-aortic velocity of < 2.5 m/sec) and an age- and sex-matched control group were enrolled.Twenty-four CHIP genes with common variants in cardiovascular disease were used to generate a next-generation sequencing panel. The primary endpoint was the CHIP detection rate between the AVS and control groups. Inverse-probability treatment weighting (IPTW) analysis was performed to adjust for differences in baseline characteristics. Results: From April 2020 to April 2022, 187 participants (125 with AVS and 62 controls) were enrolled; the mean age was 72.6 ± 8.5 yrs, and 54.5% were male. An average of 1.3CHIP variants was observed. CHIP detection, defined by a variant allele frequency (VAF) of≥ 0.5%, was similar between the groups. However, the AVS group had larger CHIP clones:49 (39.2%) participants had a VAF of ≥ 1% (vs. 13 [21.0%] in the control group; P = 0.020), and 25 (20.0%) had a VAF of ≥ 2% (vs. 4 [6.5%]; P = 0.028). AVS is independently associated with a VAF of ≥ 1% (adjusted odds ratio: 2.44, 95% confidence interval: 1.11–5.36; P = 0.027). This trend was concordant and clearer in the IPTW cohort. Conclusions Participants with AVS more commonly had larger CHIP clones than age- and sex-matched controls. Further studies are warranted to identify causality between AVS and CHIP.

OBJECTIVES: Stroke remains the second leading cause of death in Korea. This study was designed to estimate the crude, age-adjusted and age-specific incidence rates, as well as the case fatality rate of stroke, in Korea from 2011 to 2020. METHODS: We utilized data from the National Health Insurance Services from January 1, 2002 to December 31, 2020, to calculate incidence rates and 30-day and 1-year case fatality rates of stroke. Additionally, we determined sex and age-specific incidence rates and computed age-standardized incidence rates by direct standardization to the 2005 population. RESULTS: The crude incidence rate of stroke hovered around 200 (per 100,000 person-years) from 2011 to 2015, then surged to 218.4 in 2019, before marginally declining to 208.0 in 2020. Conversely, the age-standardized incidence rate consistently decreased by 25% between 2011 and 2020. When stratified by sex, the crude incidence rate increased between 2011 and 2019 for both sexes, followed by a decrease in 2020. Age-standardized incidence rates displayed a downward trend throughout the study period for both sexes. Across all age groups, the 30-day and 1-year case fatality rates of stroke consistently decreased from 2011 to 2019, only to increase in 2020. CONCLUSIONS Despite a decrease in the age-standardized incidence rate, the total number of stroke events in Korea continues to rise due to the rapidly aging population. Moreover, 2020 witnessed a decrease in incidence but an increase in case fatality rates.

OBJECTIVES: Cardiovascular diseases are a leading cause of mortality worldwide, and acute myocardial infarction (AMI) is particularly fatal condition. We evaluated the incidence and case fatality rates of AMI in Korea from 2011 to 2020. METHODS: We utilized data from the National Health Insurance Services to calculate crude, age-standardized, and age-specific incidence rates, along with 30-day and 1-year case fatality rates, of AMI from 2011 to 2020. Age-standardized incidence rates were determined using direct standardization to the 2005 population. RESULTS: The crude incidence rate of AMI per 100,000 person-years consistently increased from 44.7 in 2011 to 68.3 in 2019, before decreasing slightly to 66.2 in 2020. The age-standardized incidence rate of AMI displayed a 19% rise from 2011 to 2019, followed by a slight decline in 2020. The increasing trend for AMI incidence was more pronounced in males than in females. Both 30-day and 1-year case fatality rates remained stable among younger individuals but showed a decrease among older individuals. There was a minor surge in case fatality in 2020, particularly among recurrent AMI cases. CONCLUSIONS Over the past decade, the AMI incidence rate in Korea has consistently increased, with a slight downturn in 2020. The case fatality rate has remained relatively stable except for a minor increase in 2020. This study provides data for continuous surveillance, the implementation of targeted interventions, and the advancement of research aimed at AMI in Korea.

A 35-year-old male presented with atypical aphasia following left anterior choroidal artery infarction associated with distal internal carotid artery dissection. He presented with 1) lexical-semantic deficit without semantic impairment, 2) frequent surface errors (both surface dyslexia and dysgraphia), and 3) intact non-word reading/repetition (preserved sub-lexical route), suggesting deficit in the phonological output lexicon. Diffusion-tensor tractography analysis revealed disruption in the inferior fronto-occipital fasciculus and inferior longitudinal fasciculus, which might serve as potential subcortical neural correlates for phonological output lexicon.

Purpose: Culture-based methods for microbiological diagnosis and antibiotic susceptibility tests have limitations in the management of orofacial infections. We aimed to profile pus microbiota and identify antibiotic resistance genes (ARGs) using a culture-independent approach. Materials and Methods: Genomic DNA samples extracted from the pus specimens of two patients with orofacial abscesses were subjected to shotgun sequencing on the NovaSeq system. Taxonomic profiling and prediction of ARGs were performed directly from the metagenomic raw reads.Result: Taxonomic profiling revealed obligate anaerobic polymicrobial communities associated with infections of odontogenic origins: the microbial community of Patient 1 consisted of one predominant species (Prevotella oris 74.6%) with 27 minor species, while the sample from Patient 2 contained 3 abundant species (Porphyromonas endodontalis 33.0%; P. oris 31.6%; and Prevotella koreensis 13.4%) with five minor species. A total of 150 and 136 putative ARGs were predicted in the metagenome of each pus sample. The coverage of most predicted ARGs was less than 10%, and only the CfxA2 gene identified in Patient 1 was covered 100%. ARG analysis of the seven assembled genome/ metagenome datasets of P. oris revealed that strain C735 carried the CfxA2 gene. Conclusion A metagenomics-based approach is useful to profile predominantly anaerobic polymicrobial communities but needs further verification for reliable ARG detection.