To date 16 genes have been associated with arrhythmogenic cardiomyopathy (ACM). Mutations in these genes can lead to a broad spectrum of phenotypic expression ranging from disease affecting predominantly the right or left ventricle, to biventricular subtypes. Understanding the genetic causes of ACM is important in diagnosis and management of the disorder. This review summarizes recent advances in molecular genetics and discusses the application of next-generation sequencing technology in genetic testing in ACM.
Use of next-generation sequencing methods has resulted in the identification of novel causative variants and genes for ACM. The involvement of filamin C in ACM demonstrates the genetic overlap between ACM and other types of cardiomyopathy. Putative pathogenic variants have been detected in cadherin 2 gene, a protein involved in cell adhesion. Large genomic rearrangements in desmosome genes have been systematically investigated in a cohort of ACM patients.
Recent studies have identified novel causes of ACM providing new insights into the genetic spectrum of the disease and highlighting an overlapping phenotype between ACM and dilated cardiomyopathy. Next-generation sequencing is a useful tool for research and genetic diagnostic screening but interpretation of identified sequence variants requires caution and should be performed in specialized centres.
aCenter for Cardiovascular Genetics, Institute of Molecular Medicine, The University of Texas Health Sciences Center, Houston, Texas, USA
bCentre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, UK
Correspondence to Jennifer Karmouch, Center for Cardiovascular Genetics, Institute of Molecular Medicine, The University of Texas Health Sciences Center, 6770 Bertner Street, Suite C900A, Houston, TX 77030, USA. Tel: +1 713 500 2307; e-mail: Jennifer.Karmouch@uth.tmc.edu