PKP2 Mutations in Sudden Death From Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) and Sudden Unexpected Death With Negative Autopsy (SUDNA)

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dc.contributor.authorZhang, Mingchang
dc.contributor.authorTavora, Fabio [UNIFESP]
dc.contributor.authorOliveira, Joao Bosco
dc.contributor.authorLi, Ling
dc.contributor.authorFranco, Marcello [UNIFESP]
dc.contributor.authorFowler, David
dc.contributor.authorZhao, Ziqin
dc.contributor.authorBurke, Allen
dc.contributor.institutionFudan Univ
dc.contributor.institutionNIH
dc.contributor.institutionMessejana Heart & Lung Hosp
dc.contributor.institutionChina Univ Polit Sci & Law
dc.contributor.institutionUniv Maryland
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:17:38Z
dc.date.available2016-01-24T14:17:38Z
dc.date.issued2012-01-01
dc.description.abstractBackground: Plakophilin2 (PKP2) is a desmosome-related protein with numerous armadillo repeats and has been linked to arrhythmogenic right ventricular cardiomyopathy (ARVC). Fatal arrhythmias resulting in sudden death also occur in the absence of morphologic cardiac abnormalities at autopsy, and have been linked to ion channel mutations in a subset of cases, but so far not to PKP2.Methods and Results: We sequenced all 14 exons of PKP2 in DNA extracted from postmortem heart tissues of 25 patients dying from ARVC and 25 from sudden unexpected death with negative autopsy (SUDNA). the primers were designed using the Primer Express 3.0 software. Direct sequencing for both sense and antisense strands was performed with a BigDye Terminator DNA sequencing kit on a 3130XL Genetic Analyzer. Mutation damage prediction was made using Mutation Taster, Polyphen and SIFT software. in 6 of the 25 ARVC samples, 6 PKP2 mutations were identified, 4 of which were likely significant, and 3 of which were novel (p.N641del, p.L64PfsX22, p.G269R). in 6 of the 25 cases of SUDNA samples, 6 PKP2 mutations were identified, 3 of which were likely significant, and 4 of which were not previously described (p.P665S, p.Y217TfsX45, p.E540, p.S615T).Conclusions: PKP2 mutations are not specific for ARVC and may result in SUDNA. the link between ARVC and desmosomal mutations may not be causal but related to an association between defective desmosomal proteins and arrhythmias. (Circ J 2012; 76: 189-194)en
dc.description.affiliationFudan Univ, Shanghai Med Coll, Dept Forens Med, Shanghai 200433, Peoples R China
dc.description.affiliationNIH, Dept Lab Med, Bethesda, MD 20892 USA
dc.description.affiliationMessejana Heart & Lung Hosp, Fortaleza, Ceara, Brazil
dc.description.affiliationChina Univ Polit Sci & Law, Div Forens Med, Key Lab Evidence Sci, Beijing, Peoples R China
dc.description.affiliationUniv Maryland, Med Ctr, Baltimore, MD 21201 USA
dc.description.affiliationEscola Paulista Med, BR-04023 São Paulo, Brazil
dc.description.affiliationUnifespEscola Paulista Med, BR-04023 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent189-194
dc.identifierhttp://dx.doi.org/10.1253/circj.CJ-11-0747
dc.identifier.citationCirculation Journal. Kyoto: Japanese Circulation Soc, v. 76, n. 1, p. 189-194, 2012.
dc.identifier.doi10.1253/circj.CJ-11-0747
dc.identifier.issn1346-9843
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/34392
dc.identifier.wosWOS:000298771100032
dc.language.isoeng
dc.publisherJapanese Circulation Soc
dc.relation.ispartofCirculation Journal
dc.rightsAcesso aberto
dc.subjectArrhythmiaen
dc.subjectArrhythmogenic right ventricular cardiomyopathyen
dc.subjectDesmosomeen
dc.subjectNegative autopsyen
dc.subjectSudden deathen
dc.titlePKP2 Mutations in Sudden Death From Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) and Sudden Unexpected Death With Negative Autopsy (SUDNA)en
dc.typeArtigo
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