title: Identification of a PKP2 gene deletion in a family with arrhythmogenic right ventricular cardiomyopathy.
abstract: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary heart muscle disease characterized by progressive myocardial loss, with fibro-fatty replacement, and high frequency of ventricular arrhythmias that can lead to sudden cardiac death. ARVC is a genetically determined disorder, usually caused by point mutations in components of the cardiac desmosome. Conventional mutation screening of ARVC genes fails to detect causative mutations in about 50% of index cases, suggesting a further genetic heterogeneity. We performed a genome-wide linkage study and a copy number variations (CNVs) analysis, using high-density SNP arrays, in an ARVC family showing no mutations in any of the desmosomal genes. The CNVs analysis identified a heterozygous deletion of about 122 kb on chromosome 12p11.21, including the entire plakophilin-2 gene and shared by all affected family members. It was not listed on any of available public CNVs databases and was confirmed by quantitative real-time PCR. This is the first SNP array-based genome-wide study leading to the identification of a CNV segregating with the disease phenotype in an ARVC family. This result underscores the importance of performing additional analysis for possible genomic deletions/duplications in ARVC patients without point mutations in known disease genes.
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Ilena Egle Astrid
authors.initials: IE
authors.lastname: Li Mura
authors.forename: Barbara
authors.initials: B
authors.lastname: Bauce
authors.forename: Andrea
authors.initials: A
authors.lastname: Nava
authors.forename: Manuela
authors.initials: M
authors.lastname: Fanciulli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vazza
authors.forename: Elisa
authors.initials: E
authors.lastname: Mazzotti
authors.forename: Ilaria
authors.initials: I
authors.lastname: Rigato
authors.forename: Marzia
authors.initials: M
authors.lastname: De Bortoli
authors.forename: Giorgia
authors.initials: G
authors.lastname: Beffagna
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lorenzon
authors.forename: Martina
authors.initials: M
authors.lastname: Calore
authors.forename: Emanuela
authors.initials: E
authors.lastname: Dazzo
authors.forename: Carlo
authors.initials: C
authors.lastname: Nobile
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mostacciuolo
authors.forename: Domenico
authors.initials: D
authors.lastname: Corrado
authors.forename: Cristina
authors.initials: C
authors.lastname: Basso
authors.forename: Luciano
authors.initials: L
authors.lastname: Daliento
authors.forename: Gaetano
authors.initials: G
authors.lastname: Thiene
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rampazzo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000000981:diagnostic imaging / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D056915:DNA Copy Number Variations; D005190:Family; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage / Q000235:genetics; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D051191:Plakophilins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014463:Ultrasonography; D055815:Young Adult
chemical_list: C495337:PKP2 protein, human; D051191:Plakophilins