Browse by author
Lookup NU author(s): Eleni Mavraki, Dr Charlotte Alston, Charlotte Knowles, Jack Baines, Professor Robert Taylor
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022, The Author(s). Primary mitochondrial disease describes a diverse group of neuro-metabolic disorders characterised by impaired oxidative phosphorylation. Diagnosis is challenging; >350 genes, both nuclear and mitochondrial DNA (mtDNA) encoded, are known to cause mitochondrial disease, leading to all possible inheritance patterns and further complicated by heteroplasmy of the multicopy mitochondrial genome. Technological advances, particularly next-generation sequencing, have driven a shift in diagnostic practice from ‘biopsy first’ to genome-wide analyses of blood and/or urine DNA. This has led to the need for a reference framework for laboratories involved in mitochondrial genetic testing to facilitate a consistent high-quality service. In the United Kingdom, consensus guidelines have been prepared by a working group of Clinical Scientists from the NHS Highly Specialised Service followed by national laboratory consultation. These guidelines summarise current recommended technologies and methodologies for the analysis of mtDNA and nuclear-encoded genes in patients with suspected mitochondrial disease. Genetic testing strategies for diagnosis, family testing and reproductive options including prenatal diagnosis are outlined. Importantly, recommendations for the minimum levels of mtDNA testing for the most common referral reasons are included, as well as guidance on appropriate referrals and information on the minimal appropriate gene content of panels when analysing nuclear mitochondrial genes. Finally, variant interpretation and recommendations for reporting of results are discussed, focussing particularly on the challenges of interpreting and reporting mtDNA variants.
Author(s): Mavraki E, Labrum R, Sergeant K, Alston CL, Woodward C, Smith C, Knowles CVY, Patel Y, Hodsdon P, Baines JP, Blakely EL, Polke J, Taylor RW, Fratter C
Publication type: Article
Publication status: Published
Journal: European Journal of Human Genetics
Year: 2023
Volume: 31
Pages: 148-163
Print publication date: 01/02/2023
Online publication date: 13/12/2022
Acceptance date: 16/11/2022
Date deposited: 05/01/2023
ISSN (print): 1018-4813
ISSN (electronic): 1476-5438
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41431-022-01249-w
DOI: 10.1038/s41431-022-01249-w
Altmetrics provided by Altmetric
