Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41436-018-0046-0
Title: Defining the diagnostic effectiveness of genes for inclusion in panels: the experience of two decades of genetic testing for hypertrophic cardiomyopathy at a single center
Authors: Mazzarotto F.
Girolami F.
Boschi B.
Barlocco F.
Tomberli A.
Baldini K.
Coppini R.
Tanini I.
Bardi S.
Contini E.
Cecchi F.
Pelo E.
Cook S.A. 
Cerbai E.
Poggesi C.
Torricelli F.
Walsh R.
Olivotto I.
Keywords: Diagnostic effectiveness
HCM mimics
Hypertrophic cardiomyopathy
Mendelian HCM genetics
NGS
Issue Date: 2018
Publisher: Nature Publishing Group
Citation: Mazzarotto F., Girolami F., Boschi B., Barlocco F., Tomberli A., Baldini K., Coppini R., Tanini I., Bardi S., Contini E., Cecchi F., Pelo E., Cook S.A., Cerbai E., Poggesi C., Torricelli F., Walsh R., Olivotto I. (2018). Defining the diagnostic effectiveness of genes for inclusion in panels: the experience of two decades of genetic testing for hypertrophic cardiomyopathy at a single center. Genetics in Medicine : 1-9. ScholarBank@NUS Repository. https://doi.org/10.1038/s41436-018-0046-0
Abstract: Purpose: Genetic testing in hypertrophic cardiomyopathy (HCM) has long relied on Sanger sequencing of sarcomeric genes. The advent of next-generation sequencing (NGS) has catalyzed routine testing of additional genes of dubious HCM-causing potential. We used 19 years of genetic testing results to define a reliable set of genes implicated in Mendelian HCM and assess the value of expanded NGS panels. Methods: We dissected genetic testing results from 1,198 single-center HCM probands and devised a widely applicable score to identify which genes yield effective results in the diagnostic setting. Results: Compared with early panels targeting only fully validated sarcomeric HCM genes, expanded NGS panels allow the prompt recognition of probands with HCM-mimicking diseases. Scoring by “diagnostic effectiveness” highlighted that PLN should also be routinely screened besides historically validated genes for HCM and its mimics. Conclusion: The additive value of expanded panels in HCM genetic testing lies in the systematic screening of genes associated with HCM mimics, requiring different patient management. Only variants in a limited set of genes are highly actionable and interpretable in the clinic, suggesting that larger panels offer limited additional sensitivity. A score estimating the relative effectiveness of a given gene’s inclusion in diagnostic panels is proposed. © 2018 The Author(s)
Source Title: Genetics in Medicine
URI: http://scholarbank.nus.edu.sg/handle/10635/150623
ISSN: 10983600
DOI: 10.1038/s41436-018-0046-0
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