Mitochondrial diseases present a diagnostic challenge due to their clinical and genetic heterogeneity. Achieving comprehensive molecular diagnosis via a conventional candidate-gene approach is likely, therefore, to be labour- and cost-intensive given the expanding number of mitochondrial disease genes. The advent of whole exome sequencing (WES) and whole genome sequencing (WGS) hold the potential of higher diagnostic yields due to the universality and unbiased nature of the methods. However, these approaches are subject to the escalating challenge of variant interpretation. Thus, integration of functional ‘multi-omics’ data, such as transcriptomics, is emerging as a powerful complementary tool in the diagnosis of mitochondrial disease patients for whom extensive prior analysis of DNA sequencing has failed to return a genetic diagnosis.
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July 2018
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Cover Image
Cover Image
Mitochondria are unique organelles under the dual genetic control executed by nuclear DNA and their own genome, mitochondrial DNA. Every cell contains a population of mitochondria and multiple copies of mtDNA, carrying wild type or mutated variants (heteroplasmy). The genetic variability together with the complex regulation of multiple metabolic pathways operating in mitochondria are responsible for phenotypic variability, schematically represented in the cover image. In this issue of Essays in Biochemistry, we illustrate the biological pathways operating in mitochondria and the pathomechanisms leading to disease. We also provide an overview of the current advances in the approach to diagnosis, design of new therapies, and development of clinical trials. Image kindly provided by Caterina Garone (MRC Mitochondrial Biology Unit).
Review Article|
June 27 2018
Advancing genomic approaches to the molecular diagnosis of mitochondrial disease
Essays Biochem (2018) 62 (3): 399–408.
Article history
Received:
February 12 2018
Revision Received:
April 05 2018
Accepted:
May 08 2018
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