Lim, Albert Z.McMacken, Grace M.Rastelli, FrancescaOláhová, MonikaBaty, KarenHopton, SilaFalkous, GavinTöpf, AnaLochmüller, HannsMarini-Bettolo, ChiaraMcFarland, RobertTaylor, Robert W.2020-10-212020-10-212020Lim AZ, McMacken G, Rastelli F, Oláhová M, Baty K, Hopton S, Falkous G, Töpf A, Lochmüller H, Marini-Bettolo C, McFarland R, Taylor RW. A novel, pathogenic dinucleotide deletion in the mitochondrial MT-TY gene causing myasthenia-like features. Neuromuscul Disord. 2020; 30(8):661-8. DOI: 10.1016/j.nmd.2020.06.0080960-8966http://hdl.handle.net/10230/45538Mitochondrial 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.application/pdfeng© 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license.(http://creativecommons.org/licenses/by/4.0/)info:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.nmd.2020.06.008Congenital myasthenia syndromes (CMS)MTTY geneMitochondrial diseaseMuscle biopsymtDNA tRNA variantinfo:eu-repo/semantics/openAccess