Arrhythmogenic right ventricular cardiomyopathy: implications of next-generation sequencing in appropriate diagnosis

作者：Medeiros Domingo Argelia^*; Saguner Ardan M; Magyar Istvan; Bahr Angela; Akdis Deniz; Brunckhorst Corinna; Duru Firat; Berger Wolfgang

来源：Europace, 2017, 19(6): 1063-1069.

DOI：10.1093/europace/euw098

• Arrhythmogenic right ventricular cardiomyopathy
• Dilated cardiomyopathy
• Next-generation sequencing
• Whole-exome sequencing
• Cardiac channelopathies

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' and results system. We presented our initial results focused on 96 known cardiomyopathy and channetopathy genes. According to the 2010 task force criteria, 7/14 cases (50%) were classified as 'definite' phenotype, 4/14 (29%) were bordertine', 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.

• 出版日期2017-6
• 单位河北医科大学