title: Genetic testing of candidate genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia.
abstract: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a rare cardiac genetic disease characterized by the presence of structural alterations in the right ventricle which may cause ventricular arrhythmias and may induce sudden cardiac death. ARVC/D has been associated with mutations in genes encoding myocyte adhesion proteins. However, only 30%-50% of patients have mutations in these genes. Genetic testing is useful in obtaining a diagnosis, particularly in individuals who do not completely fulfill clinical criteria, thereby also enabling the undertaking of preventive strategies in family members. The main goal of this study was to identify mutations in candidate genes associated with intercalate disks that could be potentially involved in ARVC/D pathogenesis. We analyze a cohort of 14 Spanish unrelated patients clinically diagnosed with ARVC/D without any genetic alteration in all previously known responsible genes. Thus, a genetic screening has been performed in 7 additional potential candidate genes (ACTC1 -actin alpha cardiac muscle 1-, CDHN -cadherin 2 type 1 or N-cadherin-, CTNNA1 -catenin alpha 1-, Cx43 or GJA1 -gap junction protein alpha 1-, MVCL -Metavinculin-, MYL2 -myosin light chain 2- and MYL3 -myosin light chain 3-) by direct sequencing analysis. Our genetic analysis did not identify any disease-causing mutation. Thirty single nucleotides polymorphisms were found, six of them novel. In conclusion, our ARVC/D Spanish cohort has not shown any mutations in the analyzed candidate genes despite their involvement in formation and maintenance of the intercalated disk.
authors.affiliation: Cardiovascular Genetics Center, University of Girona-IdIBGi, C/ Pic de Peguera 11, 17003 Girona, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Campuzano
authors.forename: M
authors.initials: M
authors.lastname: Alcalde
authors.forename: P
authors.initials: P
authors.lastname: Berne
authors.forename: V
authors.initials: V
authors.lastname: Castro
authors.forename: G
authors.initials: G
authors.lastname: Guzzo
authors.forename: A
authors.initials: A
authors.lastname: Iglesias
authors.forename: L
authors.initials: L
authors.lastname: Alonso-Pulpon
authors.forename: P
authors.initials: P
authors.lastname: Garcia-Pavia
authors.forename: J
authors.initials: J
authors.lastname: Brugada
authors.forename: R
authors.initials: R
authors.lastname: Brugada
mesh_terms: D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism*; D002648:Child; D015331:Cohort Studies; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D015415:Biomarkers; D003598:Cytoskeletal Proteins