Genetic findings in patients with primary fibrotic atrial cardiomyopathy |
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| Affiliation: | 1. Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China;2. Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 22100, China;3. State Key Laboratory in Reproductive Medicine, Centre for Clinical Reproductive Medicine, Nanjing Medical University, Nanjing, 210029, China;1. Department of Cardiology, Keio University School of Medicine, Tokyo, Japan;2. Division of Diagnostic Pathology, Keio University School of Medicine, Tokyo, Japan;3. Department of Cardiology, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan;4. Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;5. Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan;1. Genetics Division, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil;2. Medicine Department, Marília University (UNIMAR), Marília, São Paulo, Brazil;3. Division of Child Neurology, Reference Center for Neuromuscular Diseases, Department of Pediatrics, CHR, University of Liège, Belgium;1. Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Japan;2. Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Japan;3. Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo, Japan;1. Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran;2. Department of Medical Genetics, Shiraz University of Medical Sciences, Shiraz, Iran;3. Comprehensive Medical Genetic Center, Shiraz University of Medical Sciences, Shiraz, Iran;4. Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran;5. Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;6. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;7. Maternal-Fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;1. Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy;2. Department of Laboratory and Infectious Diseases, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy;3. Università Cattolica Sacro Cuore, Rome, Italy;4. Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy;5. Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy;6. Department of Woman and Child Health and Public Health - Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy;1. Hacettepe University Medical School, Ankara, Turkey;2. Department of Pediatrics, Hacettepe University Medical School, Ankara, Turkey;3. Departments of Pediatric and Perinatal Pathology, Hacettepe University Medical School, Ankara, Turkey;4. Department of Radiology, Hacettepe University Medical School, Ankara, Turkey;5. Department of Pediatric Immunology, Uludag University, School of Medicine, Bursa, Turkey;6. Department of Pediatric Hematology, Hacettepe University Medical School, Ankara, Turkey;7. Department of Pediatric Immunology, Hacettepe University Medical School, Ankara, Turkey |
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| Abstract: | Primary fibrotic atrial cardiomyopathy (PF-ACM) is a novel type of cardiomyopathy characterized by primary atrial fibrosis with arrhythmogenicity and increased stroke risk without ventricular myocardium involvement. However, genetic analysis regarding PF-ACM and genotype–phenotype correlations is lacking. A cohort of PF-ACM patients was recruited and followed up. Whole-exome sequencing (WES) was applied, and genes were screened using a cardiovascular disease (CVD)-related gene panel. Echocardiography and cardiac magnetic resonance (CMR) were performed. The pathogenicity of the identified mutations was evaluated using in silico analysis. Thirty-three unrelated patients were referred for WES. Thirty-three rare variants of 19 CVD-related genes were identified in 21 patients, with 10 patients harboring more than one variation. TTN was the most frequent gene observed. Further analysis demonstrated that variations in sarcomeric (SV) or non-sarcomeric (NSV) genes were found in 16 and 10 patients, respectively. Patients carrying variants regardless of SV or NSV had larger left atrial dimensions determined by echo and larger left atrium areas determined by CMR. There was no discrepancy in disease severity between SV carriers and NSV carriers. Our genetic investigation into PF-ACM has identified several genetic culprits, providing further insight into its underlying pathophysiology and emphasizing a potential role for genetic testing for this condition. |
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| Keywords: | Primary fibrotic atrial cardiomyopathy Whole-exome sequencing CMR Echocardiography Arrhythmia |
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