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A comparative study of mutation screening of sarcomeric genes ( MYBPC3 , MYH7 , TNNT2 ) using single gene approach versus targeted gene panel next generation sequencing in a cohort of HCM patients in Egypt

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Title: A comparative study of mutation screening of sarcomeric genes ( MYBPC3 , MYH7 , TNNT2 ) using single gene approach versus targeted gene panel next generation sequencing in a cohort of HCM patients in Egypt
Authors: Kassem, HS
Walsh, R
Barton, PJ
Abdelghany, BS
Azer, RS
Buchan, R
John, S
Elguindy, A
Moharem-ElGamal, S
Badran, HM
Shehata, H
Cook, SA
Yacoub, MH
Item Type: Journal Article
Abstract: Background NGS enables simultaneous sequencing of large numbers of associated genes in genetic heterogeneous disorders, in a more rapid and cost-effective manner than traditional technologies. However there have been limited direct comparisons between NGS and more established technologies to assess the sensitivity and false negative rates of this new approach. The scope of the present manuscript is to compare variants detected in MYBPC3, MYH7 and TNNT2 genes using the stepwise dHPLC/Sanger versus targeted NGS. Methods In this study, we have analysed a group of 150 samples of patients from the Bibliotheca Alexandrina-Aswan Heart Centre National HCM program. The genetic testing was simultaneously undertaken by high throughput denaturing high-performance liquid chromatography (dHPLC) followed by Sanger based sequencing and targeted next generation deep sequencing using panel of inherited cardiac genes (ICC). The panel included over 100 genes including the 3 sarcomeric genes. Analysis of the sequencing data of the 3 genes was undertaken in a double blinded strategy. Results NGS analysis detected all pathogenic and likely pathogenic variants identified by dHPLC (50 in total, some samples had double hits). There was a 0% false negative rate for NGS based analysis. Nineteen variants were missed by dHPLC and detected by NGS, thus increasing the diagnostic yield in this co- analysed cohort from 22.0% (33/150) to 31.3% (47/150). Of interest to note that the mutation spectrum in this Egyptian HCM population revealed a high rate of homozygosity in MYBPC3 and MYH7 genes in comparison to other population studies (6/150, 4%). None of the homozygous samples were detected by dHPLC analysis. Conclusion NGS provides a useful and rapid tool to allow panoramic screening of several genes simultaneously with a high sensitivity rate amongst genes of known etiologic role allowing high throughput analysis of HCM patients and relevant control series in a less characterised population.
Issue Date: Oct-2017
Date of Acceptance: 24-May-2017
URI: http://hdl.handle.net/10044/1/98481
DOI: 10.1016/j.ejmhg.2017.05.002
ISSN: 1110-8630
Publisher: Springer Science and Business Media LLC
Start Page: 381
End Page: 387
Journal / Book Title: Egyptian Journal of Medical Human Genetics
Volume: 18
Issue: 4
Copyright Statement: © 2017 Production and hosting by Elsevier B.V. on behalf of Ain Shams University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Publication Status: Published
Open Access location: https://www.sciencedirect.com/science/article/pii/S1110863017300459
Online Publication Date: 2017-06-08
Appears in Collections:National Heart and Lung Institute
Institute of Clinical Sciences



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