Argelia Medeiros-Domingo1, Ardan M Saguner2, István Magyar3, Angela Bahr3, Deniz Akdis2, Corinna Brunckhorst2, Firat Duru2,4, Wolfgang Berger3,5,4. 1. Department of Cardiology, University Hospital Bern, 3010 Bern, Switzerland. 2. Department of Cardiology, University Heart Center Zurich, Zurich, Switzerland. 3. Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland. 4. Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland. 5. Neuroscience Center Zurich (ZNZ), University and ETH Zurich, Zurich, Switzerland.
Abstract
AIMS: To evaluate potential differences in the genetic profile of cases with 'definite', 'borderline', and 'possible' arrhythmogenic right ventricular cardiomyopathy (ARVC) phenotype by 2010 task force criteria using a custom genetic panel after whole-exome analysis. METHODS AND RESULTS: We performed whole-exome sequencing in 14 cases with the clinical diagnosis ARVC using an 'Illumina HighSeq 2000' system. We presented our initial results focused on 96 known cardiomyopathy and channelopathy genes. According to the 2010 task force criteria, 7/14 cases (50%) were classified as 'definite' phenotype, 4/14 (29%) were 'borderline', and 3/14 (21%) were diagnosed with the 'possible' phenotype. Nine out of 14 patients (64%) were males, and all were Caucasians, with an average age at genetic diagnosis of 50 ± 15 years. Among the seven cases with the 'definite' phenotype, six (86%) had a putative desmosomal mutation, while none of the seven patients with a 'possible' or borderline task force classification phenotype hosted putative mutations in desmosomal genes. Four (57%) of them had rare variants in other dilated cardiomyopathy (DCM) genes. CONCLUSIONS: Most of the patients with 'definite' ARVC phenotype by task force 2010 host mutations in desmosomal genes. Weaker ARVC phenotypes host variants/mutations in other DCM genes and result in a disease spectrum, including DCM or phenocopies of ARVC. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: To evaluate potential differences in the genetic profile of cases with 'definite', 'borderline', and 'possible' arrhythmogenic right ventricular cardiomyopathy (ARVC) phenotype by 2010 task force criteria using a custom genetic panel after whole-exome analysis. METHODS AND RESULTS: We performed whole-exome sequencing in 14 cases with the clinical diagnosis ARVC using an 'Illumina HighSeq 2000' system. We presented our initial results focused on 96 known cardiomyopathy and channelopathy genes. According to the 2010 task force criteria, 7/14 cases (50%) were classified as 'definite' phenotype, 4/14 (29%) were 'borderline', and 3/14 (21%) were diagnosed with the 'possible' phenotype. Nine out of 14 patients (64%) were males, and all were Caucasians, with an average age at genetic diagnosis of 50 ± 15 years. Among the seven cases with the 'definite' phenotype, six (86%) had a putative desmosomal mutation, while none of the seven patients with a 'possible' or borderline task force classification phenotype hosted putative mutations in desmosomal genes. Four (57%) of them had rare variants in other dilated cardiomyopathy (DCM) genes. CONCLUSIONS: Most of the patients with 'definite' ARVC phenotype by task force 2010 host mutations in desmosomal genes. Weaker ARVC phenotypes host variants/mutations in other DCM genes and result in a disease spectrum, including DCM or phenocopies of ARVC. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Deniz Akdis; Ardan M Saguner; Khooshbu Shah; Chuanyu Wei; Argelia Medeiros-Domingo; Arnold von Eckardstein; Thomas F Lüscher; Corinna Brunckhorst; H S Vincent Chen; Firat Duru Journal: Eur Heart J Date: 2017-05-14 Impact factor: 29.983
Authors: Brittney Murray; Edgar T Hoorntje; Anneline S J M Te Riele; Crystal Tichnell; Jeroen F van der Heijden; Harikrishna Tandri; Maarten P van den Berg; Jan D H Jongbloed; Arthur A M Wilde; Richard N W Hauer; Hugh Calkins; Daniel P Judge; Cynthia A James; J Peter van Tintelen; Dennis Dooijes Journal: J Cardiovasc Electrophysiol Date: 2018-05-21
Authors: Christopher M Haggerty; Cynthia A James; Hugh Calkins; Crystal Tichnell; Joseph B Leader; Dustin N Hartzel; Christopher D Nevius; Sarah A Pendergrass; Thomas N Person; Marci Schwartz; Marylyn D Ritchie; David J Carey; David H Ledbetter; Marc S Williams; Frederick E Dewey; Alexander Lopez; John Penn; John D Overton; Jeffrey G Reid; Matthew Lebo; Heather Mason-Suares; Christina Austin-Tse; Heidi L Rehm; Brian P Delisle; Daniel J Makowski; Vishal C Mehra; Michael F Murray; Brandon K Fornwalt Journal: Genet Med Date: 2017-05-04 Impact factor: 8.822