Genome-wide enhancer-associated tandem repeats are expanded in cardiomyopathy

EBioMedicine, Год журнала: 2024, Номер 101, С. 105027 - 105027

Опубликована: Фев. 27, 2024

BackgroundCardiomyopathy is a clinically and genetically heterogeneous heart condition that can lead to failure sudden cardiac death in childhood. While it has strong genetic basis, the aetiology for over 50% of cardiomyopathy cases remains unknown.MethodsIn this study, we analyse characteristics tandem repeats from genome sequence data unrelated individuals diagnosed with Canada United Kingdom (n = 1216) compare them those found general population. We perform burden analysis identify genomic epigenomic features are impacted by rare repeat expansions (TREs), enrichment functional pathways involved TRE-associated genes cardiomyopathy. use Oxford Nanopore targeted long-read sequencing validate size methylation status one most recurrent TREs. also dysregulated tissues cardiomyopathy.FindingsWe demonstrate rarely expanded population predominantly find TREs disproportionately present constrained near transcriptional start sites, have high GC content, frequently overlap active enhancer H3K27ac marks, where expansion-related DNA may reduce gene expression. silencing effect CGG DIP2B through promoter hypermethylation. show enhancer-associated loci highly expressed human cardiomyocytes differentially left ventricle cardiomyopathy.InterpretationOur findings highlight underrecognized contribution risk suggest contribute ∼4% risk.FundingGovernment Ontario (RKCY), The Canadian Institutes Health Research PJT 175329 Azrieli Foundation SickKids Catalyst Scholar Genetics University Toronto McLaughlin Centre (RKCY, SM), Ted Rogers Heart (SM), Data Sciences Institute at 175034 ENP 161429 under frame ERA PerMed (SM, RL), Stroke & Robert M Freedom Chair Cardiovascular Science Bitove Family Professorship Adult Congenital Disease (EO), Innovation (SWS, JR), (PS), Genome (PS, (PS).

Язык: Английский

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Pediatric Hypertrophic Cardiomyopathy: Exploring the Genotype‐Phenotype Association

Journal of the American Heart Association, Год журнала: 2022, Номер 11(5)

Опубликована: Фев. 18, 2022

Pediatric hypertrophic cardiomyopathy (HCM) is the most common form of in children and a leading cause sudden cardiac death. Yet, association between genotype variation, phenotype expression, adverse events pediatric HCM has not been fully elucidated. Although literature on this topic evolving adult HCM, evidence lacking. Solidifying our understanding relationship could improve risk stratification as well comprehension underlying pathophysiological characteristics HCM. In state-of-the-art review, we examine current genetic variations their with outcomes children, discuss approaches to identifying cardiovascular phenotypes explore possible avenues that death assessment.

Язык: Английский

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Clinical exome sequencing unravels the diverse spectrum of genetic heterogeneity and genotype-phenotype correlations in hypertrophic cardiomyopathy.

International Journal of Cardiology, Год журнала: 2024, Номер 411, С. 132273 - 132273

Опубликована: Июнь 15, 2024

Язык: Английский

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Desmoplakin Cardiomyopathy: Role of Inflammation and Potential Role of Disease-Modifying Therapies

Current Cardiology Reports, Год журнала: 2025, Номер 27(1)

Опубликована: Янв. 9, 2025

Язык: Английский

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Association Between Diurnal Temperature Range and Risk of Cardiomyopathy-Induced Hospitalisation in Henan, China: A Time-Series Study

Risk Management and Healthcare Policy, Год журнала: 2025, Номер Volume 18, С. 279 - 290

Опубликована: Янв. 1, 2025

The effect of the diurnal temperature range (DTR) on human health in diverse geographic areas and potential confounding factors are not fully understood. Additionally, while a robust association has been reported between cardiomyopathy (CM), evidence impact DTR is relatively limited. Here, we determined whether an exists CM hospitalisations vulnerable populations. admission data (2016-2021) were collected from seven tertiary hospitals Henan.We used GAM combined with distributed lag non-linear model (DLNM) to investigate delayed effects daily for CM.Stratified analysis was performed subgroups according sex, age, season. Attributable fractions (AF) attributable numbers (AN) employed illustrate disease burden DTR. Overall, 5,757 cases identified. admissions exhibited correlation. High (P95: 15.5 °C) low (P05: 3 increased risk, having stronger effect. Males warm seasons significantly more susceptible DTR, affected youth adults than older adults. AF AN 51% 2,936, respectively. Our results revealed significant hospitalisations, providing valuable insights development targeted prevention control measures.

Язык: Английский

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Genotype-phenotype insights of pediatric dilated cardiomyopathy

Frontiers in Pediatrics, Год журнала: 2025, Номер 13

Опубликована: Янв. 31, 2025

Dilated cardiomyopathy (DCM) in children is a severe myocardial disease characterized by enlargement of the left ventricle or both ventricles with impaired contractile function. DCM can cause adverse consequences such as heart failure, sudden death, thromboembolism, and arrhythmias. This article reviews latest advances genotype phenotype research pediatric DCM. With development gene sequencing technologies, considerable progress has been made genetic on Research shown that exhibits notable heterogeneity, over 100 DCM-related genes identified to date, primarily involving functions calcium handling, cytoskeleton, ion channels. As human genomic variations are linked phenotypes, phenotypes influenced numerous across entire genome. Children display high heterogeneity early onset, rapid progression, poor prognosis. The architecture markedly differs from adult DCM, necessitating analyses through clinical phenotyping, familial cosegregation studies, functional validation. Clarifying genotype-phenotype relationship improve diagnostic accuracy, enhance prognosis, guide follow-up treatment for genotype-positive phenotype-negative patients testing, providing new insights precision medicine. Future should further explore novel pathogenic mutations strengthen correlation facilitate precise diagnosis children.

Язык: Английский

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Evaluation of Mutation Profiles of Cardiomyopathy Patients in the Turkish Cohort

Bratislavské lekárske listy/Bratislava medical journal, Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

Язык: Английский

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On Penetrance Estimation in Family, Clinical, and Population Cohorts

Circulation Genomic and Precision Medicine, Год журнала: 2025, Номер unknown

Опубликована: Март 28, 2025

In recent years, there has been a considerable influx of publications assessing the penetrance pathogenic variants associated with monogenic diseases dominant inheritance. As large and diverse groups have sequenced, it become clear that incomplete is common to most hereditary diseases, as numerous molecular, genetic, or environmental factors can cause clinical diversity among carriers same variant. this review, we discuss some these focus on existing approaches estimating penetrance, depending data available their application different sets. We also list currently large-scale sets estimates.

Язык: Английский

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Contemporary practice and resource availability for genetic testing in paediatric hypertrophic cardiomyopathy

Journal of Medical Genetics, Год журнала: 2025, Номер unknown, С. jmg - 110696

Опубликована: Май 16, 2025

Язык: Английский

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Uncovering dendritic cell specific biomarkers for diagnosis and prognosis of cardiomyopathy using single cell RNA sequencing and comprehensive bioinformatics analysis

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Май 26, 2025

Язык: Английский

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