دورية أكاديمية
The Australian Genomics Mitochondrial Flagship: A National Program Delivering Mitochondrial Diagnoses.
| العنوان: | The Australian Genomics Mitochondrial Flagship: A National Program Delivering Mitochondrial Diagnoses. |
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| المؤلفون: | 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, Australia., Compton AG; The University of Melbourne, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia; Victorian Clinical Genetics Services, Melbourne, Australia., Baker NL; The University of Melbourne, Melbourne, Australia; Victorian Clinical Genetics Services, Melbourne, Australia., Balasubramaniam S; Sydney Children's Hospitals Network, Westmead, Australia; University of Sydney, Sydney, NSW, Australia., Best S; The University of Melbourne, Melbourne, Australia; Australian Institute of Health Innovation, Macquarie University, Sydney, 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, Australia., Boggs K; Sydney Children's Hospitals Network, Westmead, Australia., Boughtwood T; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia., Braithwaite J; Australian Institute of Health Innovation, Macquarie University, Sydney, Australia., Bratkovic D; Women's and Children's Hospital, Adelaide, Australia., Bray A; Sydney Children's Hospitals Network, Westmead, Australia., Brion MJ; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia; QIMR Berghofer Medical Research Institute, Brisbane, Australia., Burke J; Tasmanian Clinical Genetics Service, Hobart, Australia; The University of Tasmania, Hobart, Australia., Casauria S; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia., Chong B; Victorian Clinical Genetics Services, Melbourne, Australia., Coman D; Queensland Children's Hospital, Brisbane, Australia; Wesley Hospital, Brisbane, Australia; University of Queensland, Brisbane, Australia., Cowie S; Victorian Clinical Genetics Services, Melbourne, Australia., Cowley M; Children's Cancer Institute, University of New South Wales, NSW, Australia., de Silva MG; The University of Melbourne, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia; Victorian Clinical Genetics Services, Melbourne, Australia., Delatycki MB; The University of Melbourne, Melbourne, Australia; Victorian Clinical Genetics Services, Melbourne, Australia., Edwards S; Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia., Ellaway C; Sydney Children's Hospitals Network, Westmead, Australia; University of Sydney, Sydney 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, Australia., Frajman LE; The University of Melbourne, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia., Frazier AE; The University of Melbourne, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia., Gayevskiy V; Garvan Institute of Medical Research, Sydney, NSW, Australia., Ghaoui R; Royal Adelaide Hospital, Adelaide, Australia., Goel H; John Hunter Hospital, Newcastle, Australia., Goranitis I; The University of Melbourne, Melbourne, 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, Australia; Murdoch Children's Research Institute, Melbourne, Australia; Victorian Clinical Genetics Services, Melbourne, Australia; Bio 21 Molecular Science and Biotechnology Institute, Melbourne, Australia., Howting D; Harry Perkins Institute of Medical Research, Perth, Australia., Jackson MR; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, Australia., Kava MP; Perth Children's Hospital, Perth, Australia., Kemp M; The Australian e-Health Research Centre, CSIRO, Australia., King-Smith S; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, Australia., Lake NJ; Murdoch Children's Research Institute, Melbourne, Australia; Yale School of Medicine, New Haven, CT, USA., Lamont PJ; Perth Children's Hospital, Perth, Australia; Royal Perth Hospital, Perth, Australia., Lee J; The University of Melbourne, Melbourne, Australia; Victorian Clinical Genetics Services, Melbourne, Australia; Royal Children's Hospital, Melbourne, Australia., Long JC; Australian Institute of Health Innovation, Macquarie University, Sydney, Australia., MacShane M; Harry Perkins Institute of Medical Research, Perth, Australia., Madelli EO; Australian Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia., Martin EM; Sydney Children's Hospitals Network, Westmead, Australia., Marum JE; Victorian Clinical Genetics Services, Melbourne, 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, Australia., Metke A; The Australian e-Health Research Centre, CSIRO, Australia., Murray S; Mito Foundation, Sydney, Australia., Panetta J; Royal Melbourne Hospital, Melbourne, Australia., Phillips LK; Mater Hospital, South Brisbane, Australia., Quinn MCJ; Australian Genomics, Genetic Health Queensland, Brisbane, Australia., Ryan MT; Monash University, Melbourne, Australia., Schenscher S; Women's and Children's Hospital, Adelaide, 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, South Australia, Australia; Discipline of Paediatrics, University of Adelaide, Adelaide, South Australia, Australia., Stroud DA; The University of Melbourne, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia; Victorian Clinical Genetics Services, Melbourne, Australia; Bio 21 Molecular Science and Biotechnology Institute, Melbourne, Australia., Tchan MC; Faculty of Medicine and Health, University of Sydney, Australia; Department of Genetic Medicine, Westmead Hospital, Westmead, Australia., Tom M; Genetic Health Queensland, Brisbane, Australia., Wallis M; Tasmanian Clinical Genetics Service, Hobart, Australia; School of Medicine and Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia; Royal Hobart Hospital, Hobart, Australia., Ware TL; Royal Hobart Hospital, Hobart, Australia., Welch AE; Murdoch Children's Research Institute, Melbourne, Australia., Wools C; Royal Melbourne Hospital, Melbourne, Australia., Wu Y; The University of Melbourne, Melbourne, Australia., Christodoulou J; The University of Melbourne, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia; Victorian Clinical Genetics Services, Melbourne, Australia. Electronic address: john.christodoulou@mcri.edu.au., Thorburn DR; The University of Melbourne, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia; Victorian Clinical Genetics Services, Melbourne, Australia. Electronic address: david.thorburn@mcri.edu.au. |
| المصدر: | Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2024 Sep 17, pp. 101271. Date of Electronic Publication: 2024 Sep 17. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 9815831 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-0366 (Electronic) Linking ISSN: 10983600 NLM ISO Abbreviation: Genet Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2022- : [New York] : Elsevier Original Publication: Baltimore, MD : Lippincott, Williams & Wilkins, c1998- |
| مستخلص: | 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: 140 children and adults living with suspected MD were recruited using modified Nijmegen criteria (MNC) and randomized to either exome + mtDNA sequencing (ES+mtDNAseq) or genome sequencing (GS). 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%) versus European (67%) ancestry. For children, higher MNC scores correlated with increased diagnostic yield and fewer diagnoses in phenocopy genes. Additionally, three 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. (Copyright © 2024. Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: Genomics; Mitochondrial Disease; diagnosis; proteomics |
| تواريخ الأحداث: | Date Created: 20240921 Latest Revision: 20240921 |
| رمز التحديث: | 20240922 |
| DOI: | 10.1016/j.gim.2024.101271 |
| PMID: | 39305161 |
| قاعدة البيانات: | MEDLINE |
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