Distinguishing arrhythmogenic right ventricular cardiomyopathy/dysplasia-associated mutations from background genetic noise.

Details

Serval ID
serval:BIB_171219B947FF
Type
Article: article from journal or magazin.
Collection
Publications
Title
Distinguishing arrhythmogenic right ventricular cardiomyopathy/dysplasia-associated mutations from background genetic noise.
Journal
Journal of the American College of Cardiology
Author(s)
Kapplinger J.D., Landstrom A.P., Salisbury B.A., Callis T.E., Pollevick G.D., Tester D.J., Cox M.G., Bhuiyan Z., Bikker H., Wiesfeld A.C., Hauer R.N., van Tintelen J.P., Jongbloed J.D., Calkins H., Judge D.P., Wilde A.A., Ackerman M.J.
ISSN
1558-3597 (Electronic)
ISSN-L
0735-1097
Publication state
Published
Issued date
07/06/2011
Peer-reviewed
Oui
Volume
57
Number
23
Pages
2317-2327
Language
english
Notes
Publication types: Comparative Study ; Journal Article
Publication Status: ppublish
Abstract
The aims of this study were to determine the spectrum and prevalence of "background genetic noise" in the arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC) genetic test and to determine genetic associations that can guide the interpretation of a positive test result.
ARVC is a potentially lethal genetic cardiovascular disorder characterized by myocyte loss and fibrofatty tissue replacement of the right ventricle. Genetic variation among the ARVC susceptibility genes has not been systematically examined, and little is known about the background noise associated with the ARVC genetic test.
Using direct deoxyribonucleic acid sequencing, the coding exons/splice junctions of PKP2, DSP, DSG2, DSC2, and TMEM43 were genotyped for 93 probands diagnosed with ARVC from the Netherlands and 427 ostensibly healthy controls of various ethnicities. Eighty-two additional ARVC cases were obtained from published reports, and additional mutations were included from the ARVD/C Genetic Variants Database.
The overall yield of mutations among ARVC cases was 58% versus 16% in controls. Radical mutations were hosted by 0.5% of control individuals versus 43% of ARVC cases, while 16% of controls hosted missense mutations versus a similar 21% of ARVC cases. Relative to controls, mutations in cases occurred more frequently in non-Caucasians, localized to the N-terminal regions of DSP and DSG2, and localized to highly conserved residues within PKP2 and DSG2.
This study is the first to comprehensively evaluate genetic variation in healthy controls for the ARVC susceptibility genes. Radical mutations are high-probability ARVC-associated mutations, whereas rare missense mutations should be interpreted in the context of race and ethnicity, mutation location, and sequence conservation.

Keywords
Adult, Arrhythmogenic Right Ventricular Dysplasia/epidemiology, Arrhythmogenic Right Ventricular Dysplasia/genetics, Case-Control Studies, DNA Mutational Analysis, Genetic Predisposition to Disease, Genetic Testing, Humans, Middle Aged, Prevalence
Pubmed
Web of science
Open Access
Yes
Create date
01/03/2018 16:25
Last modification date
20/08/2019 13:46
Usage data