Chang, Yuchen and Rath, Emma M. and Soka, Magdalena and Singer, Emma S. and Trivedi, Gunjan and Burns, Charlotte and Austin, Rachel and Boughtwood, Tiffany and Brown, Jaye S. and Casauria, Sarah and Chong, Belinda and Cvetkovska, Jasmina and Dunwoodie, Sally L. and Lunke, Sebastian and Mattiske, Tessa and McGaughran, Julie and Pantaleo, Sarah-Jane and Quinn, Michael C.J. and Semsarian, Chris and Macciocca, Ivan and Ingles, Jodie and Fatkin, Diane and Giannoulatou, Eleni and Bagnall, Richard D. and Hill, Adam and Metke, Alejandro and Bray, Alessandra and McLean, Alison and Trainer, Alison and Mallawaarachchi, Amali and Pflaumer, Andreas and Davis, Andrew and Kelly, Andrew and Overkov, Angela and Enriquez, Annabel and Morrish, Ansley and Horton, Ari E. and Chong, Belinda and Gray, Belinda and Hanna, Bernadette and Smerdon, Carla and Herrera, Carmen and Medi, Caroline and Greer, Cassie and Ng, Chai-Ann and Burns, Charlotte and Patel, Chirag and Barnett, Chris and Semsarian, Chris and Elliott, David and Mowat, David and Winlaw, David and Das, Debjani and Howting, Denise and Garza, Denisse and Milnes, Di and Fatkin, Diane and Alankarage, Dimithu and Zentner, Dominica and Tang, Dotti and Kirk, Edwin and Giannoulatou, Eleni and Martin, Ellenore and Rath, Emma M. and Singer, Emma S. and Haan, Eric and Madelli, Evanthia O. and Collins, Felicity and Cunningham, Fiona and Chapman, Gavin and Correnti, Gemma and Hollingsworth, Georgie and Hollway, Georgina and Blue, Gillian M. and Valente, Giulia and Trivedi, Gunjan and Raju, Hariharan and Chalinor, Heather and Mountain, Helen and Sherburn, Isabella and Macciocca, Ivan and Mathew, Jacob and McNamara, James and Vandenberg, Jamie and Hayward, Janette and Smith, Janine and Davis, Jason and Brown, Jaye and Taylor, Jessica and Morwood, Jim and Vohra, Jitendra and Isbister, Joanne and Ingles, Jodie and Atherton, John J. and Rogers, Jonathan and Lipton, Jonathon and Thorpe, Jordan and Dobbins, Julia and Mansour, Julia and McGaughran, Julie and van Spaendonck-Zwarts, Karin and Waddel-Smith, Kathryn and Cox, Kathy and Wu, Kathy and Finlay, Keri and Boggs, Kirsten and Verma, Kunal and Gongolidis, Laura and Yeates, Laura and Ades, Lesley and Burnett, Leslie and Wornham, Linda and Worgan, Lisa and Soka, Magdalena and Brion, Marie-Jo and Perrin, Mark and Ryan, Mark and Sherlock, Mary-Clare and Wallis, Mathew and Haas, Mathilda and Jackson, Matilda and Perry, Matthew and Regan, Matthew and Wilson, Meredith and Bogwitz, Michael and Quinn, Michael C.J. and Milward, Michael and Tchan, Michel and Cao, Michelle and de Silva, Michelle and Vidgen, Miranda and Fine, Miriam and Al-Shinnag, Mohammad and Ohanian, Monique and Almog, Morgan and Nowak, Natalie and Dwyer, Nathan and Pachter, Nicholas and Den Elzen, Nicola and Poplawski, Nicola K. and Schonrock, Nicole and Martinez, Noelia Nunez and De Fazio, Paul and James, Paul and MacIntyre, Paul and Scuffham, Paul and Phillips, Peta and Punni, Preeti and Austin, Rachel and Pope-Couston, Rachel and Sy, Raymond and Johnson, Renee and Smyth, Renee and Bagnall, Richard D. and Harvey, Richard and Richardson, Rob Bryson and Weintraub, Robert G. and Dunwoodie, Sally L. and Casauria, Sarah and King-Smith, Sarah and Kummerfeld, Sarah and Sandaradura, Sarah and Pantaleo, Sarah-Jane and Lunke, Sebastian and Taylor, Shelby and Bodek, Simon and O’Sullivan, Sinead and Devery, Sophie and Elbracht-Leong, Stefanie and Rajagopalan, Sulekha and Mattiske, Tessa and Charitou, Theosodia and Phuong, Thuan and Boughtwood, Tiffany and Lassman, Timo and Thompson, Tina and Fear, Vanessa and Carr, Will and Chang, Yuchen and Stark, Zornitza (2026) Increased yield of genetic diagnoses in inherited heart diseases using expanded genome and RNA-splicing analyses. Genetics in Medicine, 28 (1). p. 101626. ISSN 10983600
Full text not available from this repository.Abstract
PURPOSE: The Australian Genomics Cardiovascular Disorders Flagship investigated genome sequencing as a first-line genetic test in 600 individuals with cardiomyopathy, primary arrhythmia syndromes, or congenital heart disease. Analysis of disease-specific virtual gene panels achieved a genetic diagnosis in 38% of participants. We sought to increase genetic diagnosis yields by analyzing lesser-evidenced disease genes, the mitochondrial genome, and by functional analysis of predicted splice-altering variants. METHODS: Genome sequences of 520 participants with cardiomyopathy or primary arrhythmia syndromes were reanalyzed in 572 cardiac genes and the mitochondrial genome. Participants with congenital heart disease were excluded. Variants predicted in silico to disrupt splicing were assessed with blood RNA and minigenes. RESULTS: A new genetic diagnosis was achieved in 4% (19/520) of participants, including deep intronic and mitochondrial genome variants. Ten participants had diagnostic variants in lesser evidenced disease genes; 9 had splicing variant pathogenicity functionally validated. Eleven participants had a newly identified variant of uncertain significance with high suspicion of pathogenicity, warranting clinical review. Our data supported the gene-disease association of 1 new cardiomyopathy gene, TBX20. CONCLUSION: Identifying new gene-disease relationships, maintaining contemporary gene panels, and integrating functional studies to refine splicing variant classifications increase genetic diagnoses for cardiomyopathies and primary arrhythmia syndromes.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 29 Aug 2026 02:50 |
| Last Modified: | 29 Aug 2026 02:50 |
| URI: | http://eprints.victorchang.edu.au/id/eprint/1806 |
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