Open AccessNext generation sequencing‐based copy number analysis reveals low prevalence of deletions and duplications in 46 genes associated with genetic cardiomyopathies
Author(s) -
CeyhanBirsoy Ozge,
Pugh Trevor J.,
Bowser Mark J.,
Hynes Elizabeth,
Frisella Ashley L.,
Mahanta Lisa M.,
Lebo Matt S.,
Amr Sami S.,
Funke Birgit H.
Publication year - 2016
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.187
Subject(s) - gene duplication , copy number variation , exon , genetics , gene , copy number analysis , dna sequencing , genetic testing , segmental duplication , computational biology , biology , cardiomyopathy , medicine , bioinformatics , genome , gene family , heart failure
Background Diagnostic testing for genetic cardiomyopathies has undergone dramatic changes in the last decade with next generation sequencing ( NGS ) expanding the number of genes that can be interrogated simultaneously. Exon resolution copy number analysis is increasingly incorporated into routine diagnostic testing via cytogenomic arrays and more recently via NGS . While NGS is an attractive option for laboratories that have no access to array platforms, its higher false positive rate requires weighing the added cost incurred by orthogonal confirmation against the magnitude of the increase in diagnostic yield. Although copy number variants (CNVs) have been reported in various cardiomyopathy genes, their contribution has not been systematically studied. Methods We performed single exon resolution NGS ‐based deletion/duplication analysis for up to 46 cardiomyopathy genes in >1400 individuals with cardiomyopathies including HCM , DCM , ARVC , RCM , and LVNC . Results and Conclusion Clinically significant deletions and duplications were identified in only 9 of 1425 (0.63%) individuals. The majority of those (6/9) represented intragenic events. We conclude that the added benefit of exon level deletion/duplication analysis is low for currently known cardiomyopathy genes and may not outweigh the increased cost and complexity of incorporating it into routine diagnostic testing for these disorders.