Identification of Nuclear Genetic Loci Linked to Clinical Features of the m.3243A>G Mitochondrial DNA Variant
Mitochondrial DNA (mtDNA) disorders exhibit striking clinical variability that is poorly explained by known factors such as variant heteroplasmy, age, or sex. Nuclear genetic modifiers likely play a significant role in this heterogeneity. We aimed to characterize the nature of nuclear genetic involvement for 2 common syndromic presentations of the common pathogenic mtDNA variant, m.3243A>G: mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and maternally inherited diabetes and deafness (MIDD).
Authors
- Kevin Colclough (ORCID: https://orcid.org/0000-0003-0566-4853)
- Robert D. S. Pitceathly (ORCID: https://orcid.org/0000-0002-6123-4551)
- Theodora-Dafni Michalettou (ORCID: https://orcid.org/0000-0003-2119-1099)
- Chiara Pizzamiglio (ORCID: https://orcid.org/0000-0001-5519-0313)
- Michael G. Hanna (ORCID: https://orcid.org/0000-0003-0825-4075)
- Maggie H. Shepherd (ORCID: https://orcid.org/0000-0003-2660-0955)
- Annemarie Thaele
- Thomas Klopstock (ORCID: https://orcid.org/0000-0003-2805-4652)
- Sarah J. Pickett (ORCID: https://orcid.org/0000-0002-1242-2927)
- Cornelia Kornblum (ORCID: https://orcid.org/0000-0002-0111-7281)
- Jochen Schäfer (ORCID: https://orcid.org/0009-0008-4396-6186)
- Yi Shiau Ng (ORCID: https://orcid.org/0000-0002-7591-2034)
- Catherine Feeney (ORCID: https://orcid.org/0000-0003-3189-3991)
- Douglass M. Turnbull (ORCID: https://orcid.org/0000-0002-8878-9901)
- Robert McFarland (ORCID: https://orcid.org/0000-0002-8833-2688)
- Holger Prokisch (ORCID: https://orcid.org/0000-0003-2379-6286)
- Róisín M. Boggan (ORCID: https://orcid.org/0000-0002-6592-3020)
- Michelangelo Mancuso (ORCID: https://orcid.org/0000-0003-2738-8562)
- Charlotte L. Alston (ORCID: https://orcid.org/0000-0003-2095-5464)
- Rhys Huw Thomas (ORCID: https://orcid.org/0000-0003-2062-8623)
- Andrew M. Schaefer (ORCID: https://orcid.org/0000-0001-9891-7332)
- Heather Jane Cordell (ORCID: https://orcid.org/0000-0002-1879-5572)
- Emma L. Blakely
- Imogen G. Franklin (ORCID: https://orcid.org/0009-0002-3307-2644)
- Enrico Bugiardini (ORCID: https://orcid.org/0000-0002-9709-6699)
- Robert William Taylor (ORCID: https://orcid.org/0000-0002-7768-8873)
- Cathy E. Woodward
- Lucas T. Cortés (ORCID: https://orcid.org/0009-0000-2420-2131)
- Kashyap A. Patel
- Boriana Büchner (ORCID: https://orcid.org/0000-0002-1241-3684)
- Andrew T. Hattersley
Institutions
- University of Pisa (IT)
- Queen Mary University of London (GB)
- University of Exeter (GB)
- University Hospital Bonn (DE)
- Royal Devon & Exeter NHS Foundation Trust (GB)
- Royal Victoria Infirmary (GB)
- German Center for Neurodegenerative Diseases (DE)
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- Helmholtz Zentrum München (DE)
- German Center for Pediatric and Adolescent Rheumatology (DE)
- Munich Cluster for Systems Neurology (DE)
- Institute of Human Genetics (PL)
- NIHR Exeter Clinical Research Facility (GB)
- Friedrich Baur Stiftung (DE)
- Wellcome Centre for Mitochondrial Research (GB)
- National Hospital for Neurology and Neurosurgery (GB)
- University Hospital Carl Gustav Carus (DE)
- Klinik und Poliklinik für Psychotherapie und Psychosomatik (DE)
- University College London (GB)
- Martin Luther University Halle-Wittenberg (DE)
- MRC Mitochondrial Biology Unit (GB)
- Ludwig-Maximilians-Universität München (DE)
- Newcastle University (GB)
Publication Details
- Journal
- Neurology Genetics
- Published
- 2026-07-16
- DOI
- https://doi.org/10.1212/nxg.0000000000200411
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Newcastle University
- Ludwig-Maximilians-Universität München