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Lookup NU author(s): Dr Albert Lim, Dr Grace McMacken, Francesca Rastelli, Dr Monika Olahova, Karen Baty, Sila Hopton, Gavin Falkous, Dr Ana TopfORCiD, Professor Hanns Lochmuller, Professor Chiara Marini Bettolo, Professor Bobby McFarlandORCiD, Professor Robert Taylor
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2020 The AuthorsMitochondrial DNA (mtDNA)-related diseases often pose a diagnostic challenge and require rigorous clinical and laboratory investigation. Pathogenic variants in the mitochondrial tRNA gene MT-TY, which encodes the tRNATyr, are a rare cause of mitochondrial disease. Here we describe a novel m.5860delTA anticodon variant in the MT-TY gene in a patient who initially presented with features akin to a childhood onset myasthenic syndrome. Using histochemical, immunohistochemical and protein studies we demonstrate that this mutation leads to severe biochemical defects of mitochondrial translation, which is reflected in the early onset and progressive phenotype. This case highlights the clinical overlap between mtDNA-related diseases and other neuromuscular disorders, and demonstrates the potential pitfalls in analysis of next generation sequencing results, given whole exome sequencing of a blood DNA sample failed to make a genetics diagnosis. Muscle biopsy remains an important requirement in the diagnosis of mitochondrial disease and in establishing the pathogenicity of novel mtDNA variants.
Author(s): Lim AZ, McMacken G, Rastelli F, Olahova M, Baty K, Hopton S, Falkous G, Topf A, Lochmuller H, Marini-Bettolo C, McFarland R, Taylor RW
Publication type: Article
Publication status: Published
Journal: Neuromuscular Disorders
Year: 2020
Volume: 30
Issue: 8
Pages: 661-668
Print publication date: 01/08/2020
Online publication date: 23/06/2020
Acceptance date: 17/06/2020
Date deposited: 16/11/2020
ISSN (print): 0960-8966
ISSN (electronic): 1873-2364
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.nmd.2020.06.008
DOI: 10.1016/j.nmd.2020.06.008
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