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Novel DNM1L variants impair mitochondrial dynamics through divergent mechanisms

View ORCID ProfileKelsey A Nolden, John M Egner, Jack J Collier, Oliver M Russell, Charlotte L Alston, Megan C Harwig, Michael E Widlansky, View ORCID ProfileSouphatta Sasorith, View ORCID ProfileInês A Barbosa, View ORCID ProfileAndrew GL Douglas, View ORCID ProfileJulia Baptista, Mark Walker, Deirdre E Donnelly, View ORCID ProfileAndrew A Morris, Hui Jeen Tan, Manju A Kurian, Kathleen Gorman, View ORCID ProfileSantosh Mordekar, Charu Deshpande, Rajib Samanta, Robert McFarland, View ORCID ProfileR Blake Hill, View ORCID ProfileRobert W Taylor, View ORCID ProfileMonika Oláhová  Correspondence email
Kelsey A Nolden
1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA
Roles: Conceptualization, Data curation, Software, Formal analysis, Investigation, Methodology, Writing—original draft, review, and editing
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  • ORCID record for Kelsey A Nolden
John M Egner
1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA
Roles: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing—original draft
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Jack J Collier
2Wellcome Centre for Mitochondrial Research, Newcastle University, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK
3Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada
Roles: Data curation, Software, Formal analysis, Investigation, Methodology, Writing—original draft
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Oliver M Russell
2Wellcome Centre for Mitochondrial Research, Newcastle University, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK
Roles: Software, Formal analysis, Investigation, Writing—review and editing
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Charlotte L Alston
2Wellcome Centre for Mitochondrial Research, Newcastle University, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK
4The National Health Service (NHS) Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Roles: Formal analysis and investigation
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Megan C Harwig
1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA
Roles: Software, Formal analysis, Investigation, Writing—review and editing
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Michael E Widlansky
5Department of Medicine, Division of Cardiovascular Medicine and Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI, USA
Roles: Investigation
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Souphatta Sasorith
6Laboratoire de Génétique Moléculaire, Centre Hospitalier Universitaire and PhyMedExp, INSERM U1046, CNRS UMR 9214, Montpellier, France
Roles: Software and formal analysis
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  • ORCID record for Souphatta Sasorith
Inês A Barbosa
7Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King’s College London, London, UK
Roles: Formal analysis and investigation
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  • ORCID record for Inês A Barbosa
Andrew GL Douglas
8Wessex Clinical Genetics Service, University Hospital Southampton NHS Foundation Trust, Southampton, UK
9Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
Roles: Investigation
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  • ORCID record for Andrew GL Douglas
Julia Baptista
10Peninsula Medical School, Faculty of Health, University of Plymouth, Plymouth, UK
Roles: Formal analysis and investigation
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  • ORCID record for Julia Baptista
Mark Walker
11Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
Roles: Investigation
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Deirdre E Donnelly
12Northern Ireland Regional Genetics Centre, Belfast Health and Social Care Trust, Belfast City Hospital, Belfast, UK
Roles: Investigation
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Andrew A Morris
13Willink Metabolic Unit, Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK
Roles: Investigation
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  • ORCID record for Andrew A Morris
Hui Jeen Tan
14Department of Paediatric Neurology, Royal Manchester Children’s Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester, UK
Roles: Formal analysis and investigation
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Manju A Kurian
15Developmental Neurosciences Department, Zayed Centre for Research into Rare Diseases in Children, University College London Great Ormond Street Institute of Child Health, Faculty of Population Health Sciences, London, UK
Roles: Investigation
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Kathleen Gorman
16Department of Neurology and Clinical Neurophysiology, Children’s Health Ireland at Temple Street, Dublin, Ireland
17School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
Roles: Formal analysis and investigation
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Santosh Mordekar
18Department of Paediatric Neurology, Sheffield Children’s Hospital, Sheffield, UK
Roles: Investigation
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  • ORCID record for Santosh Mordekar
Charu Deshpande
19Clinical Genetics Unit, Guys and St. Thomas’ NHS Foundation Trust, London, UK
Roles: Investigation
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Rajib Samanta
20Department of Paediatric Neurology, University Hospitals Leicester NHS Trust, Leicester, UK
Roles: Investigation
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Robert McFarland
2Wellcome Centre for Mitochondrial Research, Newcastle University, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK
4The National Health Service (NHS) Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Roles: Investigation, Writing—review and editing
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R Blake Hill
1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA
Roles: Supervision, Funding acquisition, Investigation, Writing—review and editing
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Robert W Taylor
2Wellcome Centre for Mitochondrial Research, Newcastle University, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK
4The National Health Service (NHS) Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Roles: Data curation, Supervision, Funding acquisition, Investigation, Writing—review and editing
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Monika Oláhová
2Wellcome Centre for Mitochondrial Research, Newcastle University, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK
Roles: Conceptualization, Data curation, Formal analysis, Supervision, Funding acquisition, Investigation, Methodology, Writing—original draft, review, and editing
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  • ORCID record for Monika Oláhová
  • For correspondence: monika.olahova@ncl.ac.uk
Published 1 August 2022. DOI: 10.26508/lsa.202101284
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Article Information

vol. 5 no. 12 e202101284
DOI 
https://doi.org/10.26508/lsa.202101284
PubMed 
35914810

Published By 
Life Science Alliance
Online ISSN 
2575-1077
History 
  • Received November 1, 2021
  • Revision received July 7, 2022
  • Accepted July 7, 2022
  • Published online August 1, 2022.

Copyright & Usage 
© 2022 Nolden et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).

Author Information

  1. Kelsey A Nolden1,*, Conceptualization, Data curation, Software, Formal analysis, Investigation, Methodology, Writing—original draft, review, and editing,
  2. John M Egner1,*, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing—original draft,
  3. Jack J Collier2,3, Data curation, Software, Formal analysis, Investigation, Methodology, Writing—original draft,
  4. Oliver M Russell2, Software, Formal analysis, Investigation, Writing—review and editing,
  5. Charlotte L Alston2,4, Formal analysis and investigation,
  6. Megan C Harwig1, Software, Formal analysis, Investigation, Writing—review and editing,
  7. Michael E Widlansky5, Investigation,
  8. Souphatta Sasorith6, Software and formal analysis,
  9. Inês A Barbosa7, Formal analysis and investigation,
  10. Andrew GL Douglas8,9, Investigation,
  11. Julia Baptista10, Formal analysis and investigation,
  12. Mark Walker11, Investigation,
  13. Deirdre E Donnelly12, Investigation,
  14. Andrew A Morris13, Investigation,
  15. Hui Jeen Tan14, Formal analysis and investigation,
  16. Manju A Kurian15, Investigation,
  17. Kathleen Gorman16,17, Formal analysis and investigation,
  18. Santosh Mordekar18, Investigation,
  19. Charu Deshpande19, Investigation,
  20. Rajib Samanta20, Investigation,
  21. Robert McFarland2,4, Investigation, Writing—review and editing,
  22. R Blake Hill1, Supervision, Funding acquisition, Investigation, Writing—review and editing,
  23. Robert W Taylor2,4, Data curation, Supervision, Funding acquisition, Investigation, Writing—review and editing and
  24. Monika Oláhová2⇑, Conceptualization, Data curation, Formal analysis, Supervision, Funding acquisition, Investigation, Methodology, Writing—original draft, review, and editing
  1. 1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA
  2. 2Wellcome Centre for Mitochondrial Research, Newcastle University, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK
  3. 3Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada
  4. 4The National Health Service (NHS) Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
  5. 5Department of Medicine, Division of Cardiovascular Medicine and Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI, USA
  6. 6Laboratoire de Génétique Moléculaire, Centre Hospitalier Universitaire and PhyMedExp, INSERM U1046, CNRS UMR 9214, Montpellier, France
  7. 7Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King’s College London, London, UK
  8. 8Wessex Clinical Genetics Service, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  9. 9Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
  10. 10Peninsula Medical School, Faculty of Health, University of Plymouth, Plymouth, UK
  11. 11Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  12. 12Northern Ireland Regional Genetics Centre, Belfast Health and Social Care Trust, Belfast City Hospital, Belfast, UK
  13. 13Willink Metabolic Unit, Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  14. 14Department of Paediatric Neurology, Royal Manchester Children’s Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  15. 15Developmental Neurosciences Department, Zayed Centre for Research into Rare Diseases in Children, University College London Great Ormond Street Institute of Child Health, Faculty of Population Health Sciences, London, UK
  16. 16Department of Neurology and Clinical Neurophysiology, Children’s Health Ireland at Temple Street, Dublin, Ireland
  17. 17School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
  18. 18Department of Paediatric Neurology, Sheffield Children’s Hospital, Sheffield, UK
  19. 19Clinical Genetics Unit, Guys and St. Thomas’ NHS Foundation Trust, London, UK
  20. 20Department of Paediatric Neurology, University Hospitals Leicester NHS Trust, Leicester, UK
  1. Correspondence: monika.olahova{at}ncl.ac.uk
  1. ↵* Kelsey A Nolden and John M Egner contributed equally to this work.

View Full Text

Funding

  • Wellcome Centre for Mitochondrial Research

    203105/Z/16/Z
    R McFarland, RW Taylor
  • Mitochondrial Disease Patient Cohort (UK)

    G0800674
    R McFarland, RW Taylor
  • Medical Research Council

    MR/S005021/1
    R McFarland, RW Taylor
  • UK NIHR Biomedical Research Centre

    R McFarland, RW Taylor
  • Pathology Society

    M Oláhová, RW Taylor
  • Lily Foundation

    R McFarland, M Oláhová, RW Taylor
  • Wellcome Centre for Mitochondrial Research

    203105/Z/16/Z
    OM Russell
  • National Institute for Health Research

    PDF-2018-11-ST2-021
    CL Alston
  • National Institutes of Health

    TL1TR001437; T32GM080202
    KA Nolden
  • National Institutes of Health

    R01GM067180
    RB Hill
  • National Institutes of Health

    R01HL128240
    ME Widlansky
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Pathomechanisms of DNM1L-related disease
Kelsey A Nolden, John M Egner, Jack J Collier, Oliver M Russell, Charlotte L Alston, Megan C Harwig, Michael E Widlansky, Souphatta Sasorith, Inês A Barbosa, Andrew GL Douglas, Julia Baptista, Mark Walker, Deirdre E Donnelly, Andrew A Morris, Hui Jeen Tan, Manju A Kurian, Kathleen Gorman, Santosh Mordekar, Charu Deshpande, Rajib Samanta, Robert McFarland, R Blake Hill, Robert W Taylor, Monika Oláhová
Life Science Alliance Aug 2022, 5 (12) e202101284; DOI: 10.26508/lsa.202101284

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Pathomechanisms of DNM1L-related disease
Kelsey A Nolden, John M Egner, Jack J Collier, Oliver M Russell, Charlotte L Alston, Megan C Harwig, Michael E Widlansky, Souphatta Sasorith, Inês A Barbosa, Andrew GL Douglas, Julia Baptista, Mark Walker, Deirdre E Donnelly, Andrew A Morris, Hui Jeen Tan, Manju A Kurian, Kathleen Gorman, Santosh Mordekar, Charu Deshpande, Rajib Samanta, Robert McFarland, R Blake Hill, Robert W Taylor, Monika Oláhová
Life Science Alliance Aug 2022, 5 (12) e202101284; DOI: 10.26508/lsa.202101284
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Volume 5, No. 12
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