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A novel pathogenic m.4412G>A MT-TM mitochondrial DNA variant associated with childhood-onset seizures, myopathy and bilateral basal ganglia changes

Lookup NU author(s): Dr Albert Lim, Karen Baty, Dr Langping He, Sila Hopton, Gavin Falkous, Professor Bobby McFarlandORCiD, Professor Robert Taylor



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2019 The Authors Mitochondrial DNA variants in the MT-TM (mt-tRNA Met )gene are rare, typically associated with myopathic phenotypes. We identified a novel MT-TM variant resulting in prolonged seizures with childhood-onset myopathy, retinopathy, short stature and elevated CSF lactate associated with bilateral basal ganglia changes on neuroimaging. Muscle biopsy confirmed multiple respiratory chain deficiencies and focal cytochrome c oxidase (COX)histochemical abnormalities. Next-generation sequencing of the mitochondrial genome revealed a novel m.4412G>A variant at high heteroplasmy levels in muscle that fulfils all accepted criteria for pathogenicity including segregation within single muscle fibres, thus broadening the genotypic and phenotypic landscape of mitochondrial tRNA-related disease.

Publication metadata

Author(s): Lim AZ, Blakely EL, Baty K, He L, Hopton S, Falkous G, McWilliam K, Cozens A, McFarland R, Taylor RW

Publication type: Article

Publication status: Published

Journal: Mitochondrion

Year: 2019

Volume: 47

Pages: 18-23

Print publication date: 01/07/2019

Online publication date: 22/04/2019

Acceptance date: 19/04/2019

Date deposited: 07/05/2019

ISSN (print): 1567-7249

ISSN (electronic): 1872-8278

Publisher: Elsevier BV


DOI: 10.1016/j.mito.2019.04.007


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Funder referenceFunder name
203105/Z/16/ZWellcome Trust