title: Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in the desmosomal gene desmocollin-2.
abstract: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited myocardial disorder associated with arrhythmias, heart failure, and sudden death. To date, mutations in four genes encoding major desmosomal proteins (plakoglobin, desmoplakin, plakophilin-2, and desmoglein-2) have been implicated in the pathogenesis of ARVD/C. We screened 77 probands with ARVD/C for mutations in desmocollin-2 (DSC2), a gene coding for a desmosomal cadherin. Two heterozygous mutations--a deletion and an insertion--were identified in four probands. Both mutations result in frameshifts and premature truncation of the desmocollin-2 protein. For the first time, we have identified mutations in desmocollin-2 in patients with ARVD/C, a finding that is consistent with the hypothesis that ARVD/C is a disease of the desmosome.
authors.affiliation: Department of Medicine, University College London, United Kingdom.
authors.forename: Petros
authors.initials: P
authors.lastname: Syrris
authors.forename: Deirdre
authors.initials: D
authors.lastname: Ward
authors.forename: Alison
authors.initials: A
authors.lastname: Evans
authors.forename: Angeliki
authors.initials: A
authors.lastname: Asimaki
authors.forename: Estelle
authors.initials: E
authors.lastname: Gandjbakhch
authors.forename: Srijita
authors.initials: S
authors.lastname: Sen-Chowdhry
authors.forename: William J
authors.initials: WJ
authors.lastname: McKenna
mesh_terms: D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics* / Q000503:physiopathology; D001483:Base Sequence; D018389:Codon, Nonsense / Q000235:genetics; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D051187:Desmocollins / Q000235:genetics*; D003896:Desmosomes / Q000235:genetics*; D004562:Electrocardiography; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D017384:Sequence Deletion
chemical_list: D018389:Codon, Nonsense; D017931:DNA Primers; C081561:DSC2 protein, human; D051187:Desmocollins; D004247:DNA