TY - JOUR
T1 - Genetic basis of arrhythmogenic cardiomyopathy
AU - Karmouch, Jennifer
AU - Protonotarios, Alexandros
AU - Syrris, Petros
N1 - Publisher Copyright:
© Copyright 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Purpose of review 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. Recent findings 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. Summary 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.
AB - Purpose of review 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. Recent findings 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. Summary 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.
KW - arrhythmogenic cardiomyopathy
KW - arrhythmogenic right ventricular cardiomyopathy
KW - genetics
KW - mutations
KW - next-generation sequencing
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U2 - 10.1097/HCO.0000000000000509
DO - 10.1097/HCO.0000000000000509
M3 - Review article
C2 - 29543670
AN - SCOPUS:85045564788
SN - 0268-4705
VL - 33
SP - 276
EP - 281
JO - Current opinion in cardiology
JF - Current opinion in cardiology
IS - 3
ER -