Keiko Sonoda1, Seiko Ohno2, Junichi Ozawa3, Mamoru Hayano4, Tetsuhisa Hattori5, Atsushi Kobori6, Mitsuhiko Yahata7, Isao Aburadani8, Seiichi Watanabe9, Yuichi Matsumoto10, Takeru Makiyama4, Minoru Horie11. 1. Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Molecular Biology, National Cerebral and Cardiovacular Center, Suita, Japan. 2. Department of Molecular Biology, National Cerebral and Cardiovacular Center, Suita, Japan; Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan; Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan. 3. Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 4. Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. 5. Department of Molecular Biology, National Cerebral and Cardiovacular Center, Suita, Japan; Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan. 6. Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. 7. Department of Cardiovascular Medicine, Shizuoka General Hospital, Shizuoka, Japan. 8. Department of Cardiovascular Medicine, Toyama Prefectural Central Hospital, Toyama, Japan. 9. Department of Pediatrics, Tsuchiura Kyodo General Hospital, Tsuchiura, Japan. 10. Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan. 11. Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan. Electronic address: horie@belle.shiga-med.ac.jp.
Abstract
BACKGROUND: Loss-of-function mutations in SCN5A are associated in ∼20% of Brugada syndrome (BrS) patients. Copy number variations (CNVs) have been shown to be associated with several inherited arrhythmia syndromes. OBJECTIVE: The purpose of this study was to investigate SCN5A CNVs among BrS probands. METHODS: The study cohort consisted of 151 BrS probands who were symptomatic or had a family history of BrS, sudden death, syncope, or arrhythmic diseases. We performed sequence analysis of SCN5A by the Sanger method. For detecting CNVs in SCN5A, we performed multiplex ligation-dependent probe amplification analysis of the 151 BrS probands. RESULTS: We identified pathogenic SCN5A mutations in 20 probands by the Sanger method. In 140 probands in whom multiplex ligation-dependent probe amplification was successfully performed, 4 probands were found to present different CNVs (deletion in 3 and duplication in 1). Three of them had fatal arrhythmia events; the remaining 1 was asymptomatic but had a family history. Mean age at diagnosis was 23 ± 14 years. All of the baseline 12-lead electrocardiograms showed PQ-interval prolongation. The characteristics of these 4 probands with CNVs were similar to those of the probands with mutations leading to premature truncation of the protein or missense mutations causing peak INa reduction >90%. CONCLUSION: We identified SCN5A CNVs in 2.9% of BrS probands who were symptomatic or had a family history.
BACKGROUND: Loss-of-function mutations in SCN5A are associated in ∼20% of Brugada syndrome (BrS) patients. Copy number variations (CNVs) have been shown to be associated with several inherited arrhythmia syndromes. OBJECTIVE: The purpose of this study was to investigate SCN5A CNVs among BrS probands. METHODS: The study cohort consisted of 151 BrS probands who were symptomatic or had a family history of BrS, sudden death, syncope, or arrhythmic diseases. We performed sequence analysis of SCN5A by the Sanger method. For detecting CNVs in SCN5A, we performed multiplex ligation-dependent probe amplification analysis of the 151 BrS probands. RESULTS: We identified pathogenic SCN5A mutations in 20 probands by the Sanger method. In 140 probands in whom multiplex ligation-dependent probe amplification was successfully performed, 4 probands were found to present different CNVs (deletion in 3 and duplication in 1). Three of them had fatal arrhythmia events; the remaining 1 was asymptomatic but had a family history. Mean age at diagnosis was 23 ± 14 years. All of the baseline 12-lead electrocardiograms showed PQ-interval prolongation. The characteristics of these 4 probands with CNVs were similar to those of the probands with mutations leading to premature truncation of the protein or missense mutations causing peak INa reduction >90%. CONCLUSION: We identified SCN5A CNVs in 2.9% of BrS probands who were symptomatic or had a family history.
Authors: Michelle M Monasky; Carlo Pappone; Marco Piccoli; Andrea Ghiroldi; Emanuele Micaglio; Luigi Anastasia Journal: Front Physiol Date: 2018-08-10 Impact factor: 4.566
Authors: Michelle M Monasky; Emanuele Micaglio; Giuseppe Ciconte; Sara Benedetti; Chiara Di Resta; Gabriele Vicedomini; Valeria Borrelli; Andrea Ghiroldi; Marco Piccoli; Luigi Anastasia; Vincenzo Santinelli; Maurizio Ferrari; Carlo Pappone Journal: Front Physiol Date: 2019-05-28 Impact factor: 4.566
Authors: Michelle M Monasky; Emanuele Micaglio; Daniela Giachino; Giuseppe Ciconte; Luigi Giannelli; Emanuela T Locati; Elisa Ramondini; Roberta Cotugno; Gabriele Vicedomini; Valeria Borrelli; Andrea Ghiroldi; Luigi Anastasia; Carlo Pappone Journal: Int J Mol Sci Date: 2019-11-06 Impact factor: 5.923
Authors: Emanuele Micaglio; Michelle M Monasky; Nicoletta Resta; Rosanna Bagnulo; Giuseppe Ciconte; Luigi Gianelli; Emanuela T Locati; Gabriele Vicedomini; Valeria Borrelli; Andrea Ghiroldi; Luigi Anastasia; Sara Benedetti; Chiara Di Resta; Maurizio Ferrari; Carlo Pappone Journal: Int J Mol Sci Date: 2019-10-04 Impact factor: 5.923