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Lookup NU author(s): Dr Yi NgORCiD, Dr Nichola Lax, Dr Charlotte Alston, Philippa Hepplewhite, Professor Patrick Chinnery, Catherine Feeney, Dr Steven Hardy, Dr Andrew Schaefer, Emeritus Professor Doug Turnbull, Professor Robert Taylor, Professor Bobby McFarlandORCiD, Professor Grainne Gorman
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2018 The Authors Mutations in the m.13094T>C MT-ND5 gene have been previously described in three cases of Leigh Syndrome (LS). In this retrospective, international cohort study we identified 20 clinically affected individuals (13 families) and four asymptomatic carriers. Ten patients were deceased at the time of analysis (median age of death was 10 years (range: 5·4 months−37 years, IQR = 17·9 years). Nine patients manifested with LS, one with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), and one with Leber hereditary optic neuropathy. The remaining nine patients presented with either overlapping syndromes or isolated neurological symptoms. Mitochondrial respiratory chain activity analysis was normal in five out of ten muscle biopsies. We confirmed maternal inheritance in six families, and demonstrated marked variability in tissue segregation, and phenotypic expression at relatively low blood mutant loads. Neuropathological studies of two patients manifesting with LS/MELAS showed prominent capillary proliferation, microvacuolation and severe neuronal cell loss in the brainstem and cerebellum, with conspicuous absence of basal ganglia involvement. These findings suggest that whole mtDNA genome sequencing should be considered in patients with suspected mitochondrial disease presenting with complex neurological manifestations, which would identify over 300 known pathogenic variants including the m.13094T>C.
Author(s): Ng YS, Lax NZ, Maddison P, Alston CL, Blakely EL, Hepplewhite PD, Riordan G, Meldau S, Chinnery PF, Pierre G, Chronopoulou E, Du A, Hughes I, Morris AA, Kamakari S, Chrousos G, Rodenburg RJ, Saris CGJ, Feeney C, Hardy SA, Sakakibara T, Sudo A, Okazaki Y, Murayama K, Mundy H, Hanna MG, Ohtake A, Schaefer AM, Champion MP, Turnbull DM, Taylor RW, Pitceathly RDS, McFarland R, Gorman GS
Publication type: Article
Publication status: Published
Journal: EBioMedicine
Year: 2018
Volume: 30
Pages: 86-93
Print publication date: 01/04/2018
Online publication date: 24/02/2018
Acceptance date: 12/02/2018
Date deposited: 27/03/2018
ISSN (electronic): 2352-3964
Publisher: Elsevier B.V.
URL: https://doi.org/10.1016/j.ebiom.2018.02.010
DOI: 10.1016/j.ebiom.2018.02.010
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