Coverage and diagnostic yield of Whole Exome Sequencing for the Evaluation of Cases with Dilated and Hypertrophic Cardiomyopathy

Scientific Reports
Timothy Shin Heng MakHung-Fat Tse

Abstract

Targeted next generation sequencing of gene panels has become a popular tool for the genetic diagnosis of hypertrophic (HCM) and dilated cardiomyopathy (DCM). However, it is uncertain whether the use of Whole Exome Sequencing (WES) represents a more effective approach for diagnosis of cases with HCM and DCM. In this study, we performed indirect comparisons of the coverage and diagnostic yield of WES on genes and variants related to HCM and DCM versus 4 different commercial gene panels using 40 HCM and DCM patients, assuming perfect coverage in those panels. We identified 6 pathogenic or likely pathogenic among 14 HCM patients (diagnostic yield 43%). 3 pathogenic or likely pathogenic were found among the 26 DCM patients (diagnostic yield 12%). The coverage was similar to that of four existing commercial gene panels due to the clustering of mutation within MYH7, MYBPC3, TPM1, TNT2, and TTN. Moreover, the coverage of WES appeared inadequate for TNNI3 and PLN. We conclude that most of the pathogenic variants for HCM and DCM can be found within a small number of genes which were covered by all the commercial gene panels, and the application of WES did not increase diagnostic yield.

References

Apr 16, 2011·Journal of the American College of Cardiology·Ray E Hershberger, Jill D Siegfried
Aug 1, 2013·Nature Reviews. Cardiology·Ray E HershbergerAna Morales
Aug 3, 2013·Biomarkers in Medicine·Pablo Garcia-PaviaLuis Alonso-Pulpon
Nov 16, 2013·Nucleic Acids Research·Melissa J LandrumDonna R Maglott
Feb 8, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Trevor J PughBirgit H Funke
Jun 18, 2014·European Heart Journal·Perry Elliott
Aug 5, 2014·Journal of cardiology·Kuan-Rau ChiouMin-Ji Charng
Aug 29, 2014·European Heart Journal·Jan HaasBenjamin Meder
Nov 8, 2014·Annals of Neurology·Arunkanth AnkalaMadhuri R Hegde
Nov 21, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Mark B ConsugarEric A Pierce
Jan 23, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Ahmed A AlfaresHeidi L Rehm
Jan 31, 2015·Cardiovascular Research·Carolyn Y HoYigal Pinto
Feb 5, 2015·Cell Metabolism·Elizabeth M McNallyMegan J Puckelwartz
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Mar 17, 2015·Human Mutation·Yu SunGijs W E Santen
Mar 31, 2015·Journal of the American College of Cardiology·Christopher SemsarianBarry J Maron
May 21, 2015·Journal of Biomedical Nanotechnology·Yee-Ki LeeHung-Fat Tse
Jun 1, 2015·Current Cardiology Reports·Marwan M RefaatBarry London
Jul 17, 2015·Journal of Human Genetics·Akinori Kimura
Mar 5, 2016·Nature Reviews. Cardiology·Boback Ziaeian, Gregg C Fonarow
Aug 18, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Roddy WalshHugh Watkins
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Oct 17, 2017·Circulation. Cardiovascular Genetics·Allison L CirinoUNKNOWN MedSeq Project*

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Citations

Oct 17, 2018·Pflügers Archiv : European journal of physiology·Thomas Eschenhagen, Lucie Carrier
Jul 15, 2020·Journal of Clinical Medicine·Konstantinos KolokotronisBrenda Gerull
Apr 28, 2020·European Heart Journal·Antoni Bayes-GenisJames L Januzzi
Oct 12, 2020·Current Cardiology Reports·Lisa D Wilsbacher
Dec 19, 2020·Chronic Diseases and Translational Medicine·Tian-Rui Hua, Shu-Yang Zhang
Apr 24, 2021·Circulation. Genomic and Precision Medicine·Lusha W LiangYuichi J Shimada
Jun 29, 2021·Cardiology in the Young·Xiaofei YangCuifen Zhao
Aug 14, 2021·Circulation. Genomic and Precision Medicine·Jordan E EzekianAndrew P Landstrom

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Methods Mentioned

BETA
genotyping

Software Mentioned

GATK
Genome Analysis Toolkit ( GATK )
BWA
Admera
Roche SeqCap EZ Library SR
Clinvar

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