Contribution of Cardiac Sodium Channel β-Subunit Variants to Brugada Syndrome

• Peeters Uschi

  Centre for Medical Genetics, Reproduction and Genetics; Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel)

• Scornik Fabiana

  Serra Hunter Fellow, Medical School, Universitat de Girona (UdG)

• Riuró Helena

  Department of Medical Sciences, Medical School, Universitat de Girona (UdG) Cardiovascular Genetics Center, Institut d’Investigació Biomèdica de Girona (IDIBGi)

• Pérez Guillermo

  Serra Hunter Fellow, Medical School, Universitat de Girona (UdG)

• Komurcu-Bayrak Evrim

  Department of Genetics, Institute for Experimental Medical Research, Istanbul University

• Van Malderen Sophie

  Heart Rhythm Management Centre, Department of Cardiology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB) Clinical Electrophysiology, Department of Cardiology, Thorax Center, Erasmus MC

• Pappaert Gudrun

  Heart Rhythm Management Centre, Department of Cardiology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB)

• Tarradas Anna

  Department of Medical Sciences, Medical School, Universitat de Girona (UdG) Cardiovascular Genetics Center, Institut d’Investigació Biomèdica de Girona (IDIBGi)

• Pagans Sara

  Department of Medical Sciences, Medical School, Universitat de Girona (UdG) Cardiovascular Genetics Center, Institut d’Investigació Biomèdica de Girona (IDIBGi)

• Daneels Dorien

  Centre for Medical Genetics, Reproduction and Genetics; Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel)

• Breckpot Karine

  Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel (VUB)

• Brugada Pedro

  Heart Rhythm Management Centre, Department of Cardiology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB)

• Bonduelle Maryse

  Centre for Medical Genetics, Reproduction and Genetics; Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel)

• Brugada Ramon

  Department of Medical Sciences, Medical School, Universitat de Girona (UdG) Cardiovascular Genetics Center, Institut d’Investigació Biomèdica de Girona (IDIBGi)

• Van Dooren Sonia

  Centre for Medical Genetics, Reproduction and Genetics; Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel)

抄録

Background:Brugada syndrome (BrS) is an inheritable cardiac disease associated with syncope, malignant ventricular arrhythmias and sudden cardiac death. The largest proportion of mutations in BrS is found in theSCN5Agene encoding the α-subunit of cardiac sodium channels (Nav1.5). CausalSCN5Amutations are present in 18–30% of BrS patients. The additional genetic diagnostic yield of variants in cardiac sodium channel β-subunits in BrS patients was explored and functional studies on 3 novel candidate variants were performed.Methods and Results:TheSCN1B-SCN4Bgenes were screened, which encode the 5 sodium channel β-subunits, in aSCN5Anegative BrS population (n=74). Five novel variants were detected; in silico pathogenicity prediction classified 4 variants as possibly disease causing. Three variants were selected for functional study. These variants caused only limited alterations of Nav1.5 function. Next generation sequencing of a panel of 88 arrhythmia genes could not identify other major causal mutations.Conclusions:It was hypothesized that the studied variants are not the primary cause of BrS in these patients. However, because small functional effects of these β-subunit variants can be discriminated, they might contribute to the BrS phenotype and be considered a risk factor. The existence of these risk factors can give an explanation to the reduced penetrance and variable expressivity seen in this syndrome. We therefore recommend including theSCN1-4Bgenes in a next generation sequencing-based gene panel. (Circ J 2015; 79: 2118–2129)

収録刊行物

• Circulation Journal

  Circulation Journal 79 (10), 2118-2129, 2015

  一般社団法人 日本循環器学会

キーワード

• Brugada syndrome
• Functional studies
• Patch clamp
• <i>SCN1-4B</i>

詳細情報

• CRID: 1390001205106749952
• NII論文ID: 130005099851
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-15-0164
• ISSN: 13474820
• ISSN: 13469843
• NDL書誌ID: 026749486
• PubMed: 26179811
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026749486
• Web Site: https://www.jstage.jst.go.jp/article/circj/79/10/79_CJ-15-0164/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016200701
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可