title: Arrhythmogenic right ventricular dysplasia/cardiomyopathy according to revised 2010 task force criteria with inclusion of non-desmosomal phospholamban mutation carriers.
abstract: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is frequently associated with desmosomal mutations. However, nondesmosomal mutations may be involved. The aim of this study was to assess the contribution of a phospholamban (PLN) gene mutation to ARVD/C diagnosis according to the revised 2010 task force criteria (TFC). In 142 Dutch patients (106 men, mean age 51 ± 13 years) with proven ARVD/C (fulfillment of 2010 TFC for diagnosis), 5 known desmosomal genes (PKP2, DSP, DSC2, DSG2, and JUP) and the nondesmosomal PLN gene were screened. After genetic analysis, phenotypic characteristics of desmosomal versus PLN mutation carriers were compared. In 59 of 142 patients with ARVD/C (42%), no desmosomal mutation was found. In 19 of 142 patients (13%), the PLN founder mutation c.40_42delAGA (p.Arg14del) was identified. PLN mutation carriers more often had low-voltage electrocardiograms (p = 0.004), inverted T waves in leads V4 to V6 (p <0.001), and additional structural (p = 0.007) or functional (p = 0.017) left ventricular impairment, whereas desmosomal mutation carriers had more solitary right ventricular abnormalities. The revised TFC included 21 of 142 patients with proven ARVD/C who did not meet the 1994 TFC, including 7 PLN mutation carriers. In conclusion, there is a substantial contribution of PLN mutation to ARVD/C diagnosis by the 2010 TFC. In 32% of patients (19 of 59) with genetically unexplained proven ARVD/C, this nondesmosomal mutation was found. PLN mutation carriers have ARVD/C characteristics, including important right ventricular involvement, and additionally more often low-voltage electrocardiograms, inverted T waves in the left precordial leads, and left ventricular involvement.
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands. Electronic address: j.groeneweg-4@umcutrecht.nl.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Groeneweg
authors.forename: Paul A
authors.initials: PA
authors.lastname: van der Zwaag
authors.forename: Louise R A
authors.initials: LR
authors.lastname: Olde Nordkamp
authors.forename: Hennie
authors.initials: H
authors.lastname: Bikker
authors.forename: Jan D H
authors.initials: JD
authors.lastname: Jongbloed
authors.forename: Roselie
authors.initials: R
authors.lastname: Jongbloed
authors.forename: Ans C P
authors.initials: AC
authors.lastname: Wiesfeld
authors.forename: Moniek G P J
authors.initials: MG
authors.lastname: Cox
authors.forename: Jeroen F
authors.initials: JF
authors.lastname: van der Heijden
authors.forename: Douwe E
authors.initials: DE
authors.lastname: Atsma
authors.forename: Karin
authors.initials: K
authors.lastname: de Boer
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Aryan
authors.initials: A
authors.lastname: Vink
authors.forename: Toon A B
authors.initials: TA
authors.lastname: van Veen
authors.forename: Dennis
authors.initials: D
authors.lastname: Dooijes
authors.forename: Maarten P
authors.initials: MP
authors.lastname: van den Berg
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
authors.forename: J Peter
authors.initials: JP
authors.lastname: van Tintelen
authors.forename: Richard N
authors.initials: RN
authors.lastname: Hauer
mesh_terms: D026683:Advisory Committees; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D003896:Desmosomes / Q000235:genetics*; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D014463:Ultrasonography; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D004247:DNA; D000099211:Phospholamban