Arrhythmogenic right ventricular cardiomyopathy due to a novel plakophilin 2 mutation: wide spectrum of disease in mutation carriers within a family.

Détails

ID Serval
serval:BIB_EF0D0C306F27
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Arrhythmogenic right ventricular cardiomyopathy due to a novel plakophilin 2 mutation: wide spectrum of disease in mutation carriers within a family.
Périodique
Heart rhythm
Auteur(s)
Kannankeril P.J., Bhuiyan Z.A., Darbar D., Mannens M.M., Wilde A.A., Roden D.M.
ISSN
1547-5271 (Print)
ISSN-L
1547-5271
Statut éditorial
Publié
Date de publication
08/2006
Peer-reviewed
Oui
Volume
3
Numéro
8
Pages
939-944
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article
Publication Status: ppublish
Résumé
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial disease, with male preponderance, characterized by progressive fibrofatty replacement of the right ventricle and ventricular arrhythmias. Mutations in plakophilin-2 (PKP2), a desmosomal protein, have been reported to underlie familial ARVC. We report a novel ARVC PKP2 mutation and present the clinical findings in three female mutation carriers.
We sequenced PKP2 from genomic DNA isolated from peripheral blood lymphocytes in a female proband who presented with cardiac arrest and in her four first-degree relatives. Clinical testing and diagnosis of ARVC was based on International Task Force criteria.
The proband was diagnosed with ARVC due to right ventricular enlargement and regional hypokinesis, along with repolarization abnormalities and frequent ventricular ectopy. A novel 28 bp insertion in exon 11 of the PKP2 gene was found which causes a frameshift in the coding region. This results in a change in the amino acid sequence of the protein with a premature stop codon at position 740. Of the four relatives, only the mother and younger sister were identified as mutation carriers. The mother was phenotypically normal, while the younger sister has repolarization abnormalities and frequent ventricular ectopy.
We report a novel PKP2 mutation that causes familial ARVC. All mutation carriers in this kindred group were women, and the family showed incomplete penetrance and variable expression of ARVC. Premature truncation of the plakophilin-2 protein appears to be the predominant mechanism whereby PKP2 mutations elicit the ARVC phenotype.

Mots-clé
Adolescent, Adult, Arrhythmogenic Right Ventricular Dysplasia/complications, Arrhythmogenic Right Ventricular Dysplasia/genetics, Arrhythmogenic Right Ventricular Dysplasia/pathology, Base Sequence, Electrocardiography, Electrophysiologic Techniques, Cardiac, Female, Genetic Predisposition to Disease/genetics, Genetic Testing, Heart Arrest/etiology, Heart Arrest/genetics, Heart Arrest/pathology, Heterozygote, Humans, Middle Aged, Molecular Sequence Data, Mutation, Pedigree, Phenotype, Plakophilins/genetics
Pubmed
Web of science
Création de la notice
01/03/2018 16:36
Dernière modification de la notice
24/08/2018 6:26
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