Uncovering the Dual Role of Mitochondrial and Nuclear DNA Variants in Pediatric Cardiomyopathies DOI Creative Commons
Mehmet Arda Temena, Ebru Erzurumluoğlu Gökalp, Ezgi Susam

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 20, 2023

ABSTRACT Myocardial defects, originating from disruptions in genes affecting mitochondrial proteins interacting with others, have received limited research attention. In our study involving 27 pediatric cardiomyopathy patients, we explored and nuclear for four main subtypes. Sequencing cardiomyopathy-associated patients was followed by whole mtDNA sequencing these individuals, 31 healthy controls the latter part. Our findings uncovered significant pathogenic variants: MYH7 variants three hypertrophic cases, a notable TNNC1 variant inherited interestingly an autosomal recessive manner two related restrictive TRDN left-ventricular non-compaction patient. Both FOXRED1, functioning complex I stability, MT-CO1 were detected siblings, influencing early onset together. Additionally, novel MT-RNR1 (m.684T>C) one case might explain phenotype. highlights how both nDNA could interconnected roles understanding genetics. This emphasizes that functional studies are needed to recognize this dual relationship within bioenergetic pathways cardiac muscle.

Language: Английский

Deep learning-derived 12-lead electrocardiogram-based genotype prediction for hypertrophic cardiomyopathy: a pilot study DOI Creative Commons
Laite Chen, Xia Sheng,

Chenyang Jiang

et al.

Annals of Medicine, Journal Year: 2023, Volume and Issue: 55(1)

Published: July 19, 2023

Objective: Given the psychosocial and ethical burden, patients with hypertrophic cardiomyopathy (HCMs) could benefit from establishment of genetic probability prior to test. This study aimed develop a simple tool provide genotype prediction for HCMs.Methods: A convolutional neural network (CNN) was built 12-lead electrocardiogram (ECG) 124 HCMs who underwent testing (GT), externally tested by predicting on another cohort (n = 54), compared conventional methods (the Mayo Toronto score). Using third 76), role in risk stratification explored calculating sudden cardiac death (SCD) scorers (HCM risk-SCD) across predicted genotypes. Score-CAM employed visual explanation network.Results: Overall, 80 178 (45%) were genotype-positive. ECG as input, showed an area under curve (AUC) 0.89 (95% CI, 0.83-0.96) test set, outperforming score (0.69 [95% 0.65-0.78], p < 0.001) 0.64-0.75], 0.001). The classified into two groups (predicted genotype-negative vs. genotype-positive). Compared former, genotype-positive had significantly higher HCM risk-SCD (0.04 ± 0.03 0.02, <0.01). Visualization indicated that heavily influenced limb lead.Conclusions: demonstrated promising ability assessment HCM.Patients (HCM) have severe heart failure (SCD). deep learning-derived developed, outperformed prediction, future SCD HCM.

Language: Английский

Citations

17
The Role of Multimodality Imaging in Pediatric Cardiomyopathies DOI Open Access
Sara Moscatelli, Isabella Leo, Francesco Bianco

et al.

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(14), P. 4866 - 4866

Published: July 24, 2023

Cardiomyopathies are a heterogeneous group of myocardial diseases representing the first cause heart transplantation in children. Diagnosing and classifying different phenotypes can be challenging, particularly this age group, where cardiomyopathies often overlooked until onset severe symptoms. Cardiovascular imaging is crucial diagnostic pathway, from screening to classification follow-up assessment. Several modalities have been proven helpful field, with echocardiography undoubtedly approach due its low cost, lack radiation, wide availability. However, clinical context, may not able differentiate similar complemented cardiovascular magnetic resonance. The latter allows radiation-free differentiation between unique tissue characterization, thus identifying presence extent fibrosis. Nuclear computed tomography complementary role, although they less used daily practice concern related use radiation pediatric patients. these some advantages evaluating children cardiomyopathies. This paper aims review strengths limitations each modality patients suspected or known

Language: Английский

Citations

10
Evaluation of new predictive scores for sudden cardiac death in childhood hypertrophic cardiomyopathy in a French cohort DOI Creative Commons

Pierre-Alexandre Fontanges,

Christelle Marquié,

Ali Houeijeh

et al.

Archives of cardiovascular diseases, Journal Year: 2024, Volume and Issue: 117(6-7), P. 402 - 408

Published: May 18, 2024

Hypertrophic cardiomyopathy (HCM) is rare in children, and sudden cardiac death (SCD) difficult to predict. Two prognostic scores - HCM Risk-Kids Precision Medicine for Cardiomyopathy (PRIMaCY) were developed assess the risk of SCD next 5 years children with HCM.

Language: Английский

Citations

4
Left Ventricular Systolic Dysfunction in Patients Diagnosed With Hypertrophic Cardiomyopathy During Childhood: Insights From the SHaRe Registry DOI Creative Commons
Sarah Abou Alaiwi, Thomas M. Roston, Peter Marstrand

et al.

Circulation, Journal Year: 2023, Volume and Issue: 148(5), P. 394 - 404

Published: May 25, 2023

The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes adults. Little known about the prevalence, predictors, prognosis LVSD patients diagnosed HCM as children.

Language: Английский

Citations

9
The role of diagnostic modalities in differentiating hypertensive heart disease and hypertrophic cardiomyopathy: strategies in adults for potential application in paediatrics DOI Creative Commons
Mitchell J. Wagner, Catherine Morgan,

Sara López

et al.

Cardiology in the Young, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15

Published: Jan. 24, 2025

Abstract Hypertensive heart disease and hypertrophic cardiomyopathy both lead to left ventricular hypertrophy despite differing in aetiology. Elucidating the correct aetiology of presenting can be a challenge for clinicians, especially patients with overlapping risk factors. Furthermore, drugs typically used combat hypertensive may contraindicated treatment cardiomyopathy, making diagnosis imperative. In this review, we discuss characteristics that enable clinicians discriminate two as causes hypertrophy. We summarise current literature, which is primarily focused on adult populations, containing discriminative techniques available via diagnostic modalities such electrocardiography, echocardiography, cardiac MRI, noting strategies yet applied paediatric populations. Finally, review pharmacotherapy each regard pathophysiology.

Language: Английский

Citations

0
Clinical and Genetic Heterogeneity of HCM: The Possible Role of a Deletion Involving MYH6 and MYH7 DOI Open Access

Giancarlo Mancuso,

Marina Marsan,

Paola Neroni

et al.

Genes, Journal Year: 2025, Volume and Issue: 16(2), P. 212 - 212

Published: Feb. 10, 2025

Background/Objectives: Pediatric hypertrophic cardiomyopathy (HCM) is the most common genetic myocardial disorder in children and a leading cause of sudden cardiac death (SCD) among young. Its phenotypic variability, driven by incomplete penetrance variable expressivity, presents significant challenges diagnosis clinical management. Methods: In this study, we report unique case 16-month-old female diagnosed with HCM caused rare deletion. Molecular analysis was performed using multigene panel chromosomal microarray (CMA). Results: tests identified 30 kb deletion encompassing MYH6 MYH7 genes. These genes are critical components sarcomeric architecture, known associations to other cardiomyopathies. Conclusions: This underscores heterogeneity HCM, highlighting importance considering genomic deletions involving key diagnostic evaluation.

Language: Английский

Citations

0
Cardiological Manifestations in Males and Females Affected by NAA10‐Related Disease DOI
Irene Bottillo, Chiara De Luca, Angela Cordella

et al.

American Journal of Medical Genetics Part A, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

ABSTRACT We report a family with two affected brothers presenting hypertrophic cardiomyopathy, prolonged QT interval, and intellectual disability who, after dozen years of inconclusive genetic testing, were found to share previously undescribed variant c.549delA (p.Gly184Alafs*67) in the X‐linked NAA10 gene. Their mother was heterozygous for had long history unexplained cardiac arrhythmia. ( N ‐alpha‐acetyltransferase 10) is component N‐terminal acetyltransferase A complex (also called NatA complex) necessary ‐alpha‐acetylation, among most common post‐translational protein modifications eukaryotic cells. Deleterious variants gene cause wide spectrum clinical features, recently merged under umbrella term NAA10‐related disease, mainly featuring disability, seizures, visual abnormalities. Congenital heart defects dysfunction/arrhythmias emerged as very manifestations disease both males females described medical literature. While atrial ventricular septal dominated at pediatric age sexes, observed adult females, respectively. Our observations may help early recognition ‐related based on underrecognized especially arrhythmias and/or QT, guide personalized management this neglected condition.

Language: Английский

Citations

0
Role of late gadolinium enhancement in the risk stratification of pediatric hypertrophic cardiomyopathy: based on a Chinese cohort DOI Creative Commons
Xingrui Chen,

Wei Xiangli,

Xuan Ma

et al.

The Lancet Regional Health - Western Pacific, Journal Year: 2025, Volume and Issue: 58, P. 101573 - 101573

Published: May 1, 2025

Language: Английский

Citations

0
Contemporary review on pediatric hypertrophic cardiomyopathy: insights into detection and management DOI Creative Commons
Areez Shafqat,

Abdullah Shaik,

Snygdha Koritala

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 10

Published: Jan. 4, 2024

Hypertrophic cardiomyopathy is the most common genetic cardiac disorder and defined by presence of left ventricular (LV) hypertrophy in absence a condition capable producing such magnitude hypertrophy. Over past decade, guidelines on screening, diagnostic, management protocols pediatric primary (i.e., sarcomeric) HCM have undergone significant revisions. Important revisions include changes to appropriate screening age, role MRI (CMR) diagnosis, introduction individualized SCD risk assessment models like Risk-kids PRIMaCY. This review explores open uncertainties that merit further attention, as divergent American European recommendations CMR use need for incorporating key imaging parameters into HCM-Risk Kids PRIMaCY, best method quantifying myocardial fibrosis its prognostic utility prediction HCM, devising genotype- phenotype-based exercise recommendations, heart failure medications can reverse remodeling HCM.

Language: Английский

Citations

2
Correlation of Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics DOI

Shanmugam Vippamakula,

S. Sujatha,

Pasumarthy Sree Mahalakshmi

et al.

Published: Jan. 1, 2024

Language: Английский

Citations

1