Abstract
Genomic sequencing has transformed the diagnostic approach for mitochondrial disease, yet integration into standard clinical practice is limited by access and funding. We conducted a post-implementation evaluation of genome sequencing (GS) for mitochondrial disease in Australia, which became publicly funded through the Medicare Benefits Scheme (MBS) in November 2023, to allow for broader access to testing. Test request data, including demographics, phenotypic information, and the diagnostic outcomes, were collected from November 2023 to May 2025 from the Victorian Clinical Genetics Services, the current laboratory provider of the MBS-funded service. Test uptake was 26% of predicted, with lower test rates in regional and remote areas. Over the first 19 months, 300 individuals suspected of mitochondrial disease underwent GS with a median turnaround time of 84 days (8 days–218 days). The diagnostic yield was 20%, with 56% of diagnoses in known mitochondrial disease genes. Of these, 70% (24 of 34) were in mitochondrial DNA. Seventeen diagnoses were in individuals who had prior non-diagnostic testing (exome sequencing or gene panel). We demonstrate that publicly-funded GS can deliver meaningful diagnostic outcomes for mitochondrial disease on a national scale. To maximise its impact, attention must now shift towards ensuring equitable access, particularly for regional and remote areas, and embedding sustainable mainstreaming models that support both genetic and non-genetic clinicians.
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Data availability
The variants identified in this study have been submitted to ClinVar (Submission IDs: SUB15793101, SUB15793127, SUB15796069, SUB15768047). All submitted data are publicly available.
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Acknowledgements
The authors would like to acknowledge Victorian Clinical Genetics Services for their contribution to this research.
Funding
MB is supported by a Melbourne Academic Centre for Health Clinician—Researcher Scholarship and a Mito Foundation PhD Top-Up Scholarship. The research conducted at the Murdoch Children’s Research Institute (MCRI) was supported by the Victorian Government’s Operational Infrastructure Support Program. The Chair in Genomic Medicine awarded to JC is generously supported by The Royal Children’s Hospital Foundation. Open Access funding enabled and organized by CAUL and its Member Institutions.
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Conceptualisation—MB and ZS; Data curation—MB and SL; Formal analysis—MB and SC; Investigation/Methodology—AGC, DRT, JC, MB, NB, SC, SCL, SL, and ZS; Supervision—AGC, DRT, JC, and ZS; Writing-original draft— MB; Writing-review and editing—all authors.
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This study was conducted in accordance with the revised Declaration of Helsinki and following the Australian National Health and Medical Research Council statement of ethical conduct in research involving humans. This study has Human Research Ethics Committee approval (QA/104560/RCHM-2024).
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Ball, M., Baker, N., Lim, S.C. et al. Mainstreaming genomic testing for mitochondrial disease in Australia. Eur J Hum Genet (2026). https://doi.org/10.1038/s41431-026-02053-6
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DOI: https://doi.org/10.1038/s41431-026-02053-6
