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Pathological findings of myocardium in a patient with cardiac conduction defect associated with an SCN5A mutation

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Abstract

A 16-year-old Japanese man was admitted to our hospital because of syncope during exercise. His father and his younger brother had permanent pacemaker implantation because of sick sinus syndrome. Several examinations revealed first-degree atrioventricular block, complete right bundle branch block, sick sinus syndrome, and ventricular tachycardia with normal cardiac function. As no abnormalities were evident on coronary angiography, right ventricular endomyocardial biopsy was performed. It showed myocardial disarrangement and lipofuscin accumulation in hypertrophic myocytes. Moreover, electron microscopy showed a few degenerative myocytes, Z-band streaming, disarrangement, increased small capillaries with Weibel-Palade bodies in endothelial cells, and endothelial proliferations. Genetic analysis of the proband, his father, and his younger brother revealed a missense mutation, D1275N, in SCN5A, a gene which encodes sodium ion channel protein, are related to cardiomyopathy and arrhythmia. The proband was diagnosed with a cardiac conduction defect (CCD) and underwent permanent pacemaker implantation. These pathological findings suggest various myocardial changes presented in CCD patients with a missense mutation, D1275N, in SCN5A.

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References

  1. Wilde AAM, Amin AS (2018) Clinical spectrum of SCN5A mutations: long QT syndrome, Brugada syndrome, and cardiomyopathy. JACC Clin Electrophysiol 4:569–579

    Article  PubMed  Google Scholar 

  2. McNair WP, Sinagra G, Taylor MR, Di Lenarda A, Ferguson DA, Salcedo EE, Slavov D, Zhu X, Caldwell JH, Mestroni L; Familial Cardiomyopathy Registry Research Group (2011) SCN5A mutations associate with arrhythmic dilated cardiomyopathy and commonly localize to the voltage-sensing mechanism. J Am Coll Cardiol 57:2160–2168

    Article  Google Scholar 

  3. Ferrans VJ (1980) Cardiovascular system, lymphoreticular and hematopoietic system. In: Johannssen JV (ed) Electron microscope in human medicine. McGraw-Hill International Book Company, New York, pp 4–83

    Google Scholar 

  4. Ebina T, Hoshi N, Kobayashi M, Kawamura K, Nanjo H, Sugita A, Sugiyama T, Masuda H, Xu C (2002) Physiological angiogenesis in electrically stimulated skeletal muscle in rabbits: characterization of capillary sprouting by ultrastructural 3-D reconstruction study. Pathol Int 52:702–712

    Article  PubMed  Google Scholar 

  5. Folkman J (1984) Angiogenesis. In: Jaffe EA (ed) Biology of endothelial cells. Marinus Nifhoff Publishers, Boston, pp 412–418

    Chapter  Google Scholar 

  6. Coronel R, Casini S, Koopmann TT, Wilms-Schopman FJ, Verkerk AO, de Groot JR, Bhuiyan Z, Bezzina CR, Veldkamp MW, Linnenbank AC, van der Wal AC, Tan HL, Brugada P, Wilde AA, de Bakker JM (2005) Right ventricular fibrosis and conduction delay in a patient with clinical signs of Brugada syndrome: a combined electrophysiological, genetic, histopathologic, and computational study. Circulation 112:2769–2777

    Article  PubMed  Google Scholar 

  7. Frustaci A, Priori SG, Pieroni M, Chimenti C, Napolitano C, Rivolta I, Sanna T, Bellocci F, Russo MA (2005) Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome. Circulation 112:3680–3687

    Article  PubMed  Google Scholar 

  8. Watanabe H, Ohkubo K, Watanabe I, Matsuyama TA, Ishibashi-Ueda H, Yagihara N, Shimizu W, Horie M, Minamino T, Makita N (2013) SCN5A mutation associated with ventricular fibrillation, early repolarization, and concealed myocardial abnormalities. Int J Cardiol 165:e21–e23

    Article  PubMed  Google Scholar 

  9. Zhang T, Yong SL, Drinko JK, Popović ZB, Shryock JC, Belardinelli L, Wang QK (2011) LQTS mutation N1325S in cardiac sodium channel gene SCN5A causes cardiomyocyte apoptosis, cardiac fibrosis and contractile dysfunction in mice. Int J Cardiol 147:239–245

    Article  PubMed  Google Scholar 

  10. Royer A, van Veen TA, Le Bouter S, Marionneau C, Griol-Charhbili V, Léoni AL, Steenman M, van Rijen HV, Demolombe S, Goddard CA, Richer C, Escoubet B, Jarry-Guichard T, Colledge WH, Gros D, de Bakker JM, Grace AA, Escande D, Charpentier F (2005) Mouse model of SCN5A-linked hereditary Lenègre’s disease: age-related conduction slowing and myocardial fibrosis. Circulation 111:1738–1746

    Article  CAS  PubMed  Google Scholar 

  11. Hesse M, Kondo CS, Clark RB, Su L, Allen FL, Geary-Joo CT, Kunnathu S, Severson DL, Nygren A, Giles WR, Cross JC (2007) Dilated cardiomyopathy is associated with reduced expression of the cardiac sodium channel Scn5a. Cardiovasc Res 75:498–509

    Article  CAS  PubMed  Google Scholar 

  12. Watanabe H, Yang T, Stroud DM, Lowe JS, Harris L, Atack TC, Wang DW, Hipkens SB, Leake B, Hall L, Kupershmidt S, Chopra N, Magnuson MA, Tanabe N, Knollmann BC, George AL Jr, Roden DM (2011) Striking In vivo phenotype of a disease-associated human SCN5A mutation producing minimal changes in vitro. Circulation 124:1001–1011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Maron BJ, Ferrans VJ, Roberts WC (1975) Ultrastructural features of degenerated cardiac muscle cells in patients with cardiac hypertrophy. Am J Pathol 79:387–434

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Davis DG, Nelson KR, Markesbery WR (1990) Congenital myopathy and cardiomyopathy with identical ultrastructural changes. Arch Neurol 47:1141–1144

    Article  CAS  PubMed  Google Scholar 

  15. Mitrut R, Stepan AE, Pirici D (2018) Histopathological aspects of the myocardium in dilated cardiomyopathy. Curr Health Sci J 44:243–249

    CAS  PubMed  PubMed Central  Google Scholar 

  16. McCormack JJ, Lopes da Silva M, Ferraro F, Patella F, Cutler DF (2017) Weibel-Palade bodies at a glance. J Cell Sci 130:3611–3617

    Article  CAS  PubMed  Google Scholar 

  17. Valentijn KM, Sadler JE, Valentijn JA, Voorberg J, Eikenboom J (2011) Functional architecture of Weibel-Palade bodies. Blood 117:5033–5043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Mai J, Wang F, Qiu Q, Tang B, Lin Y, Luo N, Yuan W, Wang X, Chen Q, Wang J, Chen Y (2016) Tachycardia pacing induces myocardial neovascularization and mobilizes circulating endothelial progenitor cells partly via SDF-1 pathway in canines. Heart Vessels 31:230–240

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Hiroaki Kawano, Masaki Kohno, Mitsuaki Ishijima, Satoki Fukae & Koji Maemura

  2. Faculty of Science and Engineering, Waseda University, Tokyo, Japan

    Koichi Kawamura

  3. Omics Research Center, National Cerebral and Cardiovascular Center, Suita, Japan

    Taisuke Ishikawa & Naomasa Makita

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  1. Hiroaki Kawano
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  2. Koichi Kawamura
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  3. Masaki Kohno
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  4. Mitsuaki Ishijima
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  8. Koji Maemura
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Correspondence to Hiroaki Kawano.

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Kawano, H., Kawamura, K., Kohno, M. et al. Pathological findings of myocardium in a patient with cardiac conduction defect associated with an SCN5A mutation. Med Mol Morphol 54, 259–264 (2021). https://doi.org/10.1007/s00795-021-00283-9

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  • DOI: https://doi.org/10.1007/s00795-021-00283-9

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