Advantages and perils of clinical whole-exome and whole-genome sequencing in cardiomyopathy.
File(s)CDT_review_WESWGS_accepted.pdf (1.4 MB)
Accepted version
Author(s)
Mazzarotto, Francesco
Olivotto, Iacopo
Walsh, Roddy
Type
Journal Article
Abstract
As the price of next-generation sequencing keeps decreasing, cost is becoming a less important discriminator for diagnostic laboratories in choosing the preferred type of approach to genetic testing. Genome-wide sequencing strategies will plausibly become the standard first-tier tools for genetic testing, with the potential for deeper understanding of the genetic architecture of cardiomyopathies and discovery of the underlying aetiology in the many patients in whom the genetic cause remains elusive. Routine usage of extended sequencing assays will also enable "genetic-first diagnostics", particularly for those patients affected with syndromic conditions of unclear genetic origin, often resulting in costly and distressing diagnostic odysseys before reaching a diagnosis. However, access to genome-wide data for all patients will need to be managed with rigour and caution by (cardiovascular) genetic professionals to avoid erroneous variant pathogenicity assertions and over-reporting uncertain findings, both damaging scenarios to patients and their family members. Researchers will also be required to adopt robust methods to demonstrate novel genetic associations with disease, given the high "narrative potential" of such large datasets and the dangers of generating further false positive associations (that have previously blighted the field of cardiac genetics). Here, we discuss advantages and dangers associated with the routine adoption of whole-exome (and whole-genome) sequencing in diagnostic facilities and in the research setting in the context of cardiomyopathies but relevant to several other conditions.
Date Issued
2020-04
Date Acceptance
2020-02-01
Citation
Cardiovascular Drugs and Therapy, 2020, 34, pp.241-253
ISSN
0920-3206
Publisher
Springer (part of Springer Nature)
Start Page
241
End Page
253
Journal / Book Title
Cardiovascular Drugs and Therapy
Volume
34
Copyright Statement
© Springer Science+Business Media, LLC, part of Springer Nature 2020. The final publication is available at Springer via http://doi.org/10.1007/s10557-020-06948-4
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/32080787
PII: 10.1007/s10557-020-06948-4
Subjects
Cardiomyopathy
Clinical genetic testing
Whole-exome sequencing
Whole-genome sequencing
Publication Status
Published online
Coverage Spatial
United States
Date Publish Online
2020-02-21