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Recent advances in understanding the molecular genetic basis of mitochondrial disease

Lookup NU author(s): Dr Kyle Thompson, Jack Collier, Ruth Glasgow, Dr Fiona Robertson, Dr Angela Pyle, Dr Charlotte Alston, Dr Monika Olahova, Professor Bobby McFarlandORCiD, Professor Robert Taylor



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2019 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM Mitochondrial disease is hugely diverse with respect to associated clinical presentations and underlying genetic causes, with pathogenic variants in over 300 disease genes currently described. Approximately half of these have been discovered in the last decade due to the increasingly widespread application of next generation sequencing technologies, in particular unbiased, whole exome—and latterly, whole genome sequencing. These technologies allow more genetic data to be collected from patients with mitochondrial disorders, continually improving the diagnostic success rate in a clinical setting. Despite these significant advances, some patients still remain without a definitive genetic diagnosis. Large datasets containing many variants of unknown significance have become a major challenge with next generation sequencing strategies and these require significant functional validation to confirm pathogenicity. This interface between diagnostics and research is critical in continuing to expand the list of known pathogenic variants and concomitantly enhance our knowledge of mitochondrial biology. The increasing use of whole exome sequencing, whole genome sequencing and other “omics” techniques such as transcriptomics and proteomics will generate even more data and allow further interrogation and validation of genetic causes, including those outside of coding regions. This will improve diagnostic yields still further and emphasizes the integral role that functional assessment of variant causality plays in this process—the overarching focus of this review.

Publication metadata

Author(s): Thompson K, Collier JJ, Glasgow RIC, Robertson FM, Pyle A, Blakely EL, Alston CL, Olahova M, McFarland R, Taylor RW

Publication type: Review

Publication status: Published

Journal: Journal of Inherited Metabolic Disease

Year: 2020

Volume: 43

Issue: 1

Pages: 36-50

Print publication date: 20/01/2020

Online publication date: 25/04/2019

Acceptance date: 24/04/2019

ISSN (print): 0141-8955

ISSN (electronic): 1573-2665

Publisher: John Wiley and Sons Inc.


DOI: 10.1002/jimd.12104

PubMed id: 31021000