TOP3A pathogenic variants presenting as dilated cardiomyopathy and heart failure in three pediatric cases
- 1Department of Cardiology, Shanghai Children’s Medical Centre, Shanghai Jiao Tong University School of Medicine
- 2Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine
- 3Department of Genetic Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine
Abstract
Dilated cardiomyopathy (DCM) is the most prevalent form of cardiomyopathy in children, characterized by left ventricle dilation and impaired systolic function. The etiology critically influences clinical trajectory and prognosis. Mitochondrial disorders represent a rare but increasingly recognized cause of DCM. Herein, we report three pediatric patients, diagnosed with early-onset DCM at ages of 8, 9, and 8, who progressed rapidly to end stage heart failure, resulting in two fatalities and one cardiac transplantation. Whole exome sequencing (WES) analysis identified compound heterozygous TOP3A pathogenic variants in all three cases, accompanied by reduced mitochondrial DNA copy number. Therefore, this report expands the recognized etiologies of childhood DCM and delineates a severe cardiac phenotype within the TOP3A pathogenic variant spectrum. Trial Registration: Registered at Chinese Clinical Trial Registry (ChiCTR2600117173). Registered 20/01/2026. Retrospectively registered.
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BibTeX
@article{zhang2026top3a,
title = {{TOP3A pathogenic variants presenting as dilated cardiomyopathy and heart failure in three pediatric cases}},
author = {Yipu Zhang and Jiayi Xu and Wenxiu Chan and Hao Chen and Jinjin Wu and Ying Guo and Ru-en Yao and Lijun Fu},
journal = {BMC Pediatrics},
year = {2026},
month = jul,
doi = {10.1186/s12887-026-07361-w},
url = {https://doi.org/10.1186/s12887-026-07361-w},
note = {CC BY},
}
RIS
TY - JOUR
TI - TOP3A pathogenic variants presenting as dilated cardiomyopathy and heart failure in three pediatric cases
AU - Yipu Zhang
AU - Jiayi Xu
AU - Wenxiu Chan
AU - Hao Chen
AU - Jinjin Wu
AU - Ying Guo
AU - Ru-en Yao
AU - Lijun Fu
PY - 2026
DA - 2026/07/01
JO - BMC Pediatrics
DO - 10.1186/s12887-026-07361-w
UR - https://doi.org/10.1186/s12887-026-07361-w
AB - Dilated cardiomyopathy (DCM) is the most prevalent form of cardiomyopathy in children, characterized by left ventricle dilation and impaired systolic function. The etiology critically influences clinical trajectory and prognosis. Mitochondrial disorders represent a rare but increasingly recognized cause of DCM. Herein, we report three pediatric patients, diagnosed with early-onset DCM at ages of 8, 9, and 8, who progressed rapidly to end stage heart failure, resulting in two fatalities and one cardiac transplantation. Whole exome sequencing (WES) analysis identified compound heterozygous TOP3A pathogenic variants in all three cases, accompanied by reduced mitochondrial DNA copy number. Therefore, this report expands the recognized etiologies of childhood DCM and delineates a severe cardiac phenotype within the TOP3A pathogenic variant spectrum. Trial Registration: Registered at Chinese Clinical Trial Registry (ChiCTR2600117173). Registered 20/01/2026. Retrospectively registered.
SN - 1471-2431
ER -