Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy

Autor: Roberts, J. D., Herkert, J. C., Rutberg, J., Nikkel, S. M., Wiesfeld, A. C. P., Dooijes, D., Gow, R. M., van Tintelen, J. P., Gollob, M. H.
Přispěvatelé: Cardiovascular Centre (CVC)
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Clinical Genetics, 83(5), 452-456. Wiley
ISSN: 0009-9163
Popis: Roberts JD, Herkert JC, Rutberg J, Nikkel SM, Wiesfeld ACP, Dooijes D, Gow RM, van Tintelen JP, Gollob MH. Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy. Clin Genet 2013: 83: 452-456. (C) John Wiley & Sons A/S. Published by Blackwell Publishing Ltd, 2012 Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin-2 (PKP2) identified with microarray analysis and/or multiplex ligation-dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis.
Databáze: OpenAIRE
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