title: Absence of a Primary Role for SCN10A Mutations in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.
abstract: Prior reports have identified associations between SCN10A and cardiac disorders, such as atrial fibrillation and Brugada syndrome. We evaluated SCN10A in 151 probands with ARVD/C. In this cohort, 10 putatively pathogenic SCN10A variants were identified, including a novel frameshift insertion. Despite a known role for the encoded protein in peripheral nerve function, the proband with the frameshift variant had no discernible neurological abnormalities. Arrhythmic phenotypes were not different between those with a rare variant in SCN10A and those without. The prevalence of rare variants in SCN10A was similar among ARVD/C probands with and without a desmosome mutation and similar among healthy Caucasian controls. These results indicate the absence of a primary role for SCN10A mutations in ARVD/C.
authors.affiliation: Department of Medicine/Cardiology, Division of Cardiology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Suite 1049, Baltimore, MD, 21205, USA.|Department of Medicine, Division of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Anneline S J M
authors.initials: AS
authors.lastname: Te Riele
authors.affiliation: Department of Medicine/Cardiology, Division of Cardiology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Suite 1049, Baltimore, MD, 21205, USA.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: James
authors.affiliation: Department of Medicine/Cardiology, Division of Cardiology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Suite 1049, Baltimore, MD, 21205, USA.
authors.forename: Brittney
authors.initials: B
authors.lastname: Murray
authors.affiliation: Department of Medicine/Cardiology, Division of Cardiology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Suite 1049, Baltimore, MD, 21205, USA.
authors.forename: Crystal
authors.initials: C
authors.lastname: Tichnell
authors.affiliation: Department of Medicine/Cardiology, Division of Cardiology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Suite 1049, Baltimore, MD, 21205, USA.
authors.forename: Nuria
authors.initials: N
authors.lastname: Amat-Alarcon
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Burks
authors.affiliation: Department of Medicine/Cardiology, Division of Cardiology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Suite 1049, Baltimore, MD, 21205, USA.
authors.forename: Harikrishna
authors.initials: H
authors.lastname: Tandri
authors.affiliation: Department of Medicine/Cardiology, Division of Cardiology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Suite 1049, Baltimore, MD, 21205, USA.
authors.forename: Hugh
authors.initials: H
authors.lastname: Calkins
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Polydefkis
authors.affiliation: Department of Medicine/Cardiology, Division of Cardiology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Suite 1049, Baltimore, MD, 21205, USA. djudge@jhmi.edu.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
mesh_terms: D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000235:genetics*; D010641:Phenotype; D012307:Risk Factors; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568317:SCN10A protein, human
keywords: Arrhythmogenic right ventricular cardiomyopathy; SCN10A; Sudden cardiac death