The Australian Genomics Mitochondrial Flagship: A national program delivering mitochondrial diagnoses.

Autor:	Rius R; Centre for Population Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Centre for Population Genomics, Garvan Institute of Medical Research, and UNSW Sydney, Sydney, NSW, Australia; The University of Melbourne, Melbourne, VIC, Australia., Compton AG; The University of Melbourne, Melbourne, VIC, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia; Victorian Clinical Genetics Services, Melbourne, VIC, Australia., Baker NL; The University of Melbourne, Melbourne, VIC, Australia; Victorian Clinical Genetics Services, Melbourne, VIC, Australia., Balasubramaniam S; Sydney Children's Hospitals Network, Westmead, NSW, Australia; University of Sydney, Sydney, NSW, Australia., Best S; The University of Melbourne, Melbourne, VIC, Australia; Australian Institute of Health Innovation, Macquarie University, Sydney, NSW, Australia; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Victorian Comprehensive Cancer Centre, Melbourne, VIC, Australia; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia., Bhattacharya K; Sydney Children's Hospitals Network, Westmead, NSW, Australia., Boggs K; Sydney Children's Hospitals Network, Westmead, NSW, Australia., Boughtwood T; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia., Braithwaite J; Australian Institute of Health Innovation, Macquarie University, Sydney, NSW, Australia., Bratkovic D; Women's and Children's Hospital, Adelaide, SA, Australia., Bray A; Sydney Children's Hospitals Network, Westmead, NSW, Australia., Brion MJ; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Burke J; Tasmanian Clinical Genetics Service, Hobart, Australia; The University of Tasmania, Hobart, TAS, Australia., Casauria S; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia., Chong B; Victorian Clinical Genetics Services, Melbourne, VIC, Australia., Coman D; Queensland Children's Hospital, Brisbane, QLD, Australia; Wesley Hospital, Brisbane, QLD, Australia; University of Queensland, Brisbane, QLD, Australia., Cowie S; Victorian Clinical Genetics Services, Melbourne, VIC, Australia., Cowley M; Children's Cancer Institute, University of New South Wales, NSW, Australia., de Silva MG; The University of Melbourne, Melbourne, VIC, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia; Victorian Clinical Genetics Services, Melbourne, VIC, Australia., Delatycki MB; The University of Melbourne, Melbourne, VIC, Australia; Victorian Clinical Genetics Services, Melbourne, VIC, Australia., Edwards S; Harry Perkins Institute of Medical Research, University of Western Australia, Perth, WA, Australia., Ellaway C; S1ydney Children's Hospitals Network, Westmead, NSW, Australia; University of Sydney, Sydney, NSW, Australia., Fahey MC; Royal Melbourne Hospital, Melbourne, VIC, Australia., Finlay K; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia., Fletcher J; Royal Adelaide Hospital, Adelaide, SA, Australia., Frajman LE; The University of Melbourne, Melbourne, VIC, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia., Frazier AE; The University of Melbourne, Melbourne, VIC, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia., Gayevskiy V; Garvan Institute of Medical Research, Sydney, NSW, Australia., Ghaoui R; Royal Adelaide Hospital, Adelaide, SA, Australia., Goel H; John Hunter Hospital, Newcastle, NSW, Australia., Goranitis I; The University of Melbourne, Melbourne, VIC, Australia; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia., Haas M; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia., Hock DH; The University of Melbourne, Melbourne, VIC, Australia; Bio 21 Molecular Science and Biotechnology Institute, Melbourne, VIC, Australia; Department of Genetic Medicine, Westmead Hospital, Westmead, NSW, Australia., Howting D; Harry Perkins Institute of Medical Research, Perth, WA, Australia., Jackson MR; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, SA, Australia., Kava MP; Perth Children's Hospital, Perth, WA, Australia., Kemp M; The Australian e-Health Research Centre, CSIRO, Brisbane, QLD, Australia., King-Smith S; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, SA, Australia., Lake NJ; Murdoch Children's Research Institute, Melbourne, VIC, Australia; Yale School of Medicine, New Haven, CT., Lamont PJ; Perth Children's Hospital, Perth, WA, Australia; Royal Perth Hospital, Perth, WA, Australia., Lee J; The University of Melbourne, Melbourne, VIC, Australia; Victorian Clinical Genetics Services, Melbourne, VIC, Australia; Royal Children's Hospital, Melbourne, VIC, Australia., Long JC; Australian Institute of Health Innovation, Macquarie University, Sydney, NSW, Australia., MacShane M; Harry Perkins Institute of Medical Research, Perth, WA, Australia., Madelli EO; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia., Martin EM; Sydney Children's Hospitals Network, Westmead, NSW, Australia., Marum JE; Victorian Clinical Genetics Services, Melbourne, VIC, Australia; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Mattiske T; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia., McGill J; Queensland Children's Hospital, Brisbane, QLD, Australia., Metke A; The Australian e-Health Research Centre, CSIRO, Brisbane, QLD, Australia., Murray S; Mito Foundation, Sydney, NSW, Australia., Panetta J; Royal Melbourne Hospital, Melbourne, VIC, Australia., Phillips LK; Mater Hospital, South Brisbane, QLD, Australia., Quinn MCJ; Australian Genomics, Genetic Health Queensland, Brisbane, QLD, Australia., Ryan MT; Monash University, Melbourne, VIC, Australia., Schenscher S; Women's and Children's Hospital, Adelaide, SA, Australia., Simons C; Centre for Population Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Centre for Population Genomics, Garvan Institute of Medical Research, and UNSW Sydney, Sydney, NSW, Australia., Smith N; Department of Neurology and Clinical Neurophysiology, Women's and Children's Hospital, Adelaide, SA, Australia; Discipline of Paediatrics, University of Adelaide, Adelaide, SA, Australia., Stroud DA; The University of Melbourne, Melbourne, VIC, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia; Victorian Clinical Genetics Services, Melbourne, VIC, Australia; Bio 21 Molecular Science and Biotechnology Institute, Melbourne, VIC, Australia., Tchan MC; Department of Genetic Medicine, Westmead Hospital, Westmead, NSW, Australia; Faculty of Medicine and Health, University of Sydney, NSW, Australia., Tom M; Genetic Health Queensland, Brisbane, QLD, Australia., Wallis M; Tasmanian Clinical Genetics Service, Hobart, TAS, Australia; School of Medicine and Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia; Royal Hobart Hospital, Hobart, TAS, Australia., Ware TL; Royal Hobart Hospital, Hobart, TAS, Australia., Welch AE; Murdoch Children's Research Institute, Melbourne, VIC, Australia., Wools C; Royal Melbourne Hospital, Melbourne, VIC, Australia., Wu Y; The University of Melbourne, Melbourne, VIC, Australia., Christodoulou J; The University of Melbourne, Melbourne, VIC, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia; Victorian Clinical Genetics Services, Melbourne, VIC, Australia. Electronic address: john.christodoulou@mcri.edu.au., Thorburn DR; The University of Melbourne, Melbourne, VIC, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia; Victorian Clinical Genetics Services, Melbourne, VIC, Australia. Electronic address: david.thorburn@mcri.edu.au.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2024 Sep 19, pp. 101271. Date of Electronic Publication: 2024 Sep 19.
DOI:	10.1016/j.gim.2024.101271
Abstrakt:	Purpose: Families living with mitochondrial diseases (MD) often endure prolonged diagnostic journeys and invasive testing, yet many remain without a molecular diagnosis. The Australian Genomics Mitochondrial Flagship, comprising clinicians, diagnostic, and research scientists, conducted a prospective national study to identify the diagnostic utility of singleton genomic sequencing using blood samples. Methods: A total of 140 children and adults living with suspected MD were recruited using modified Nijmegen criteria (MNC) and randomized to either exome + mitochondrial DNA (mtDNA) sequencing or genome sequencing. Results: Diagnostic yield was 55% (n = 77) with variants in nuclear (n = 37) and mtDNA (n = 18) MD genes, as well as phenocopy genes (n = 22). A nuclear gene etiology was identified in 77% of diagnoses, irrespective of disease onset. Diagnostic rates were higher in pediatric-onset (71%) than adult-onset (31%) cases and comparable in children with non-European (78%) vs European (67%) ancestry. For children, higher MNC scores correlated with increased diagnostic yield and fewer diagnoses in phenocopy genes. Additionally, 3 adult patients had a mtDNA deletion discovered in skeletal muscle that was not initially identified in blood. Conclusion: Genomic sequencing from blood can simplify the diagnostic pathway for individuals living with suspected MD, especially those with childhood onset diseases and high MNC scores. Competing Interests: Conflict of Interest John Christodoulou is an approved pathology provider for Victorian Clinical Genetics Services. (Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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