Integrated multi-omics for rapid rare disease diagnosis on a national scale.

Autor:	Lunke S; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.; Australian Genomics, Melbourne, Victoria, Australia., Bouffler SE; Australian Genomics, Melbourne, Victoria, Australia., Patel CV; Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia., Sandaradura SA; Sydney Children's Hospitals Network - Westmead, Sydney, New South Wales, Australia.; Children's Hospital Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia., Wilson M; Sydney Children's Hospitals Network - Westmead, Sydney, New South Wales, Australia.; Children's Hospital Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia., Pinner J; Sydney Children's Hospitals Network - Randwick, Sydney, New South Wales, Australia.; Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia., Hunter MF; Monash Genetics, Monash Health, Melbourne, Victoria, Australia.; Department of Paediatrics, Monash University, Melbourne, Victoria, Australia., Barnett CP; Paediatric and Reproductive Genetics Unit, Women's and Children's Hospital, North Adelaide, South Australia, Australia.; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia.; Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia., Wallis M; Tasmanian Clinical Genetics Service, Tasmanian Health Service, Hobart, Tasmania, Australia.; School of Medicine and Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia., Kamien B; Genetic Services of Western Australia, Perth, Western Australia, Australia., Tan TY; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia., Freckmann ML; Department of Clinical Genetics, The Canberra Hospital, Canberra, Australian Capital Territory, Australia., Chong B; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Phelan D; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Francis D; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Kassahn KS; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia.; Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia., Ha T; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia.; Centre for Cancer Biology, An alliance between SA Pathology and the University of South Australia, Adelaide, South Australia.; UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia., Gao S; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia., Arts P; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia.; Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia.; Centre for Cancer Biology, An alliance between SA Pathology and the University of South Australia, Adelaide, South Australia.; UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia., Jackson MR; Australian Genomics, Melbourne, Victoria, Australia.; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia., Scott HS; Australian Genomics, Melbourne, Victoria, Australia.; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia.; Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia.; Centre for Cancer Biology, An alliance between SA Pathology and the University of South Australia, Adelaide, South Australia.; UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia., Eggers S; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Rowley S; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Boggs K; Australian Genomics, Melbourne, Victoria, Australia.; Sydney Children's Hospitals Network - Westmead, Sydney, New South Wales, Australia.; Sydney Children's Hospitals Network - Randwick, Sydney, New South Wales, Australia., Rakonjac A; Australian Genomics, Melbourne, Victoria, Australia.; Sydney Children's Hospitals Network - Westmead, Sydney, New South Wales, Australia.; Sydney Children's Hospitals Network - Randwick, Sydney, New South Wales, Australia., Brett GR; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia., de Silva MG; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Springer A; Monash Genetics, Monash Health, Melbourne, Victoria, Australia.; Department of Paediatrics, Monash University, Melbourne, Victoria, Australia., Ward M; Genetic Services of Western Australia, Perth, Western Australia, Australia., Stallard K; Paediatric and Reproductive Genetics Unit, Women's and Children's Hospital, North Adelaide, South Australia, Australia., Simons C; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Conway T; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Halman A; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Van Bergen NJ; Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Sikora T; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Semcesen LN; Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia., Stroud DA; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Compton AG; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Thorburn DR; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Bell KM; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Sadedin S; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.; Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., North KN; Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.; Australian Genomics, Melbourne, Victoria, Australia.; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Christodoulou J; Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.; Australian Genomics, Melbourne, Victoria, Australia.; Children's Hospital Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia.; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Stark Z; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia. zornitza.stark@vcgs.org.au.; Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia. zornitza.stark@vcgs.org.au.; Australian Genomics, Melbourne, Victoria, Australia. zornitza.stark@vcgs.org.au.
Jazyk:	angličtina
Zdroj:	Nature medicine [Nat Med] 2023 Jul; Vol. 29 (7), pp. 1681-1691. Date of Electronic Publication: 2023 Jun 08.
DOI:	10.1038/s41591-023-02401-9
Abstrakt:	Critically ill infants and children with rare diseases need equitable access to rapid and accurate diagnosis to direct clinical management. Over 2 years, the Acute Care Genomics program provided whole-genome sequencing to 290 families whose critically ill infants and children were admitted to hospitals throughout Australia with suspected genetic conditions. The average time to result was 2.9 d and diagnostic yield was 47%. We performed additional bioinformatic analyses and transcriptome sequencing in all patients who remained undiagnosed. Long-read sequencing and functional assays, ranging from clinically accredited enzyme analysis to bespoke quantitative proteomics, were deployed in selected cases. This resulted in an additional 19 diagnoses and an overall diagnostic yield of 54%. Diagnostic variants ranged from structural chromosomal abnormalities through to an intronic retrotransposon, disrupting splicing. Critical care management changed in 120 diagnosed patients (77%). This included major impacts, such as informing precision treatments, surgical and transplant decisions and palliation, in 94 patients (60%). Our results provide preliminary evidence of the clinical utility of integrating multi-omic approaches into mainstream diagnostic practice to fully realize the potential of rare disease genomic testing in a timely manner. (© 2023. The Author(s).)
Databáze:	MEDLINE
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