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A novel, pathogenic dinucleotide deletion in the mitochondrial MT-TY gene causing myasthenia-like features

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, Dr 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.

Publication metadata

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


DOI: 10.1016/j.nmd.2020.06.008


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Funder referenceFunder name
203105/Z/16/ZWellcome Trust
Medical Research Council (MRC) International Centre fir Genomic Medicine in Neuromuscular Disease
Newcastle University Centre for Ageing and Vitality
Newcastle upon Tyne Hospitals NHS Foundation Trust
UK NHS Specialist Commissioners
the Lily Foundation