Mitochondrial Diseases: A Diagnostic Revolution

Katherine R Schon; Thiloka Ratnaike; Jelle van den Ameele; Rita Horvath; Patrick F Chinnery

doi:10.1016/j.tig.2020.06.009

Mitochondrial Diseases: A Diagnostic Revolution

Trends Genet. 2020 Sep;36(9):702-717. doi: 10.1016/j.tig.2020.06.009. Epub 2020 Jul 13.

Authors

Katherine R Schon¹, Thiloka Ratnaike², Jelle van den Ameele¹, Rita Horvath³, Patrick F Chinnery⁴

Affiliations

¹ Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; Medical Research Council (MRC) Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
² Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; Medical Research Council (MRC) Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; Department of Paediatrics, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
³ Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
⁴ Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; Medical Research Council (MRC) Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK. Electronic address: pfc25@cam.ac.uk.

PMID: 32674947
DOI: 10.1016/j.tig.2020.06.009

Abstract

Mitochondrial disorders have emerged as a common cause of inherited disease, but are traditionally viewed as being difficult to diagnose clinically, and even more difficult to comprehensively characterize at the molecular level. However, new sequencing approaches, particularly whole-genome sequencing (WGS), have dramatically changed the landscape. The combined analysis of nuclear and mitochondrial DNA (mtDNA) allows rapid diagnosis for the vast majority of patients, but new challenges have emerged. We review recent discoveries that will benefit patients and families, and highlight emerging questions that remain to be resolved.

Keywords: genetic diagnosis; mitochondrial disease; molecular diagnostics; mtDNA mutation; whole-genome sequencing.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

DNA, Mitochondrial / analysis*
DNA, Mitochondrial / genetics*
Genome, Mitochondrial*
Humans
Mitochondrial Diseases / diagnosis*
Mitochondrial Diseases / genetics
Mutation*
Whole Genome Sequencing / methods*

Substances

DNA, Mitochondrial

Abstract

Publication types

MeSH terms

Substances

Grants and funding