The role of genetic testing in diagnosis and care of inherited cardiac conditions in a specialised multidisciplinary clinic.
Full text not available from this repository.Item Type: | Article |
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Status: | Published |
Official URL: | https://doi.org/10.1186/s13073-022-01149-0 |
Journal or Publication Title: | Genome Medicine |
Volume: | 14 |
Number: | 1 |
Date: | 28 December 2022 |
Divisions: | Cardio Genomics Molecular Cardiology |
Depositing User: | General Admin |
Identification Number: | 10.1186/s13073-022-01149-0 |
ISSN: | 1756-994X |
Date Deposited: | 15 Mar 2023 23:46 |
Abstract: | Abstract Methods: A retrospective audit of 1697 consecutive, unrelated probands referred to a specialised, multidisciplinary clinic between 2002 and 2020 was performed. A concordant clinical and genetic diagnosis was considered solved. Cases were classified as likely monogenic based on a score comprising a positive family history, young age at onset, and severe phenotype, whereas low-scoring cases were considered to have a likely complex aetiology. The impact of a genetic diagnosis was evaluated. Results: A total of 888 probands fulfilled the inclusion criteria, and genetic testing identified likely pathogenic or pathogenic (LP/P) variants in 330 individuals (37%) and suspicious variants of uncertain significance (VUS) in 73 (8%). Research-focused efforts identified 46 (5%) variants, missed by conventional genetic testing. Where a variant was identified, this changed or clarified the final diagnosis in a clinically useful way for 51 (13%). The yield of suspicious VUS across ancestry groups ranged from 15 to 20%, compared to only 10% among Europeans. Even when the clinical diagnosis was uncertain, those with the most monogenic disease features had the greatest diagnostic yield from genetic testing. Conclusions: Research-focused efforts can increase the diagnostic yield by up to 5%. Where a variant is identified, this will have clinical utility beyond family screening in 13%. We demonstrate the value of genomics in reaching an overall diagnosis and highlight inequities based on ancestry. Acknowledging our incomplete understanding of disease phenotypes, we propose a framework for prioritising likely monogenic cases to solve their underlying cause of disease. |
Creators: | Creators Email Stafford, Fergus UNSPECIFIED Krishnan, Neesha UNSPECIFIED Richardson, Ebony UNSPECIFIED Butters, Alexandra UNSPECIFIED Hespe, Sophie UNSPECIFIED Burns, Charlotte UNSPECIFIED Gray, Belinda UNSPECIFIED Medi, Caroline UNSPECIFIED Nowak, Natalie UNSPECIFIED Isbister, Julia C. UNSPECIFIED Raju, Hariharan UNSPECIFIED Richmond, David UNSPECIFIED Ryan, Mark P. UNSPECIFIED Singer, Emma S. UNSPECIFIED Sy, Raymond W. UNSPECIFIED Yeates, Laura UNSPECIFIED Bagnall, Richard D. UNSPECIFIED Semsarian, Christopher UNSPECIFIED Ingles, Jodie UNSPECIFIED |
Last Modified: | 15 Mar 2023 23:46 |
URI: | https://eprints.centenary.org.au/id/eprint/1427 |
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