Minoche, Andre E. and Horvat, Claire and Johnson, Renee and Gayevskiy, Velimir and Morton, Sarah U and Drew, Alexander P and Woo, Kerhan and Statham, Aaron L. and Lundie, Ben and Bagnall, Richard D and Ingles, Jodie and Semsarian, Christopher and Seidman, Jonathan G and Seidman, Christine E and Dinger, Marcel E and Cowley, Mark J and Fatkin, Diane (2018) Genome sequencing as a first-line genetic test in familial dilated cardiomyopathy. Genetics in Medicine, ePub. ISSN 1098-3600 (Not OA)
Full text not available from this repository.Abstract
PURPOSE:
We evaluated genome sequencing (GS) as an alternative to multigene panel sequencing (PS) for genetic testing in dilated cardiomyopathy (DCM).
METHODS:
Forty-two patients with familial DCM underwent PS and GS, and detection rates of rare single-nucleotide variants and small insertions/deletions in panel genes were compared. Loss-of-function variants in 406 cardiac-enriched genes were evaluated, and an assessment of structural variation was performed.
RESULTS:
GS provided broader and more uniform coverage than PS, with high concordance for rare variant detection in panel genes. GS identified all PS-identified pathogenic or likely pathogenic variants as well as two additional likely pathogenic variants: one was missed by PS due to low coverage, the other was a known disease-causing variant in a gene not included on the panel. No loss-of-function variants in the extended gene set met clinical criteria for pathogenicity. One BAG3 structural variant was classified as pathogenic.
CONCLUSION:
Our data support the use of GS for genetic testing in DCM, with high variant detection accuracy and a capacity to identify structural variants. GS provides an opportunity to go beyond suites of established disease genes, but the incremental yield of clinically actionable variants is limited by a paucity of genetic and functional evidence for DCM association.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 09 Jul 2018 23:26 |
| Last Modified: | 11 Jan 2019 00:38 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/742 |
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