Identification of a PKP2 gene deletion in a family with arrhythmogenic right ventricular cardiomyopathy.
Eur J Hum Genet
; 21(11): 1226-31, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-23486541
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Deleção de Genes
/
Displasia Arritmogênica Ventricular Direita
/
Placofilinas
Tipo de estudo:
Diagnostic_studies
Limite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Eur J Hum Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Itália