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Pathogenic variants in MT-ATP6: A United Kingdom–based mitochondrial disease cohort study

Lookup NU author(s): Dr Yi NgORCiD, Dr Mika Martikainen, Professor Grainne Gorman, Dr Alasdair Blain, Dr Andrew Schaefer, Dr Charlotte Alston, Dr Albert Lim, Professor Patrick Chinnery, Professor Rita HorvathORCiD, Dr Victoria Nesbitt, Professor Michael Hanna, Dr Robert Pitceathly, Professor Robert Taylor, Emeritus Professor Doug Turnbull, Professor Bobby McFarlandORCiD



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


© 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.Distinct clinical syndromes have been associated with pathogenic MT-ATP6 variants. In this cohort study, we identified 125 individuals (60 families) including 88 clinically affected individuals and 37 asymptomatic carriers. Thirty-one individuals presented with Leigh syndrome and 7 with neuropathy ataxia retinitis pigmentosa. The remaining 50 patients presented with variable nonsyndromic features including ataxia, neuropathy, and learning disability. We confirmed maternal inheritance in 39 families and demonstrated that tissue segregation patterns and phenotypic threshold are variant dependent. Our findings suggest that MT-ATP6–related mitochondrial DNA disease is best conceptualized as a mitochondrial disease spectrum disorder and should be routinely included in genetic ataxia and neuropathy gene panels. ANN NEUROL 2019.

Publication metadata

Author(s): Ng YS, Martikainen MH, Gorman GS, Blain A, Bugiardini E, Bunting A, Schaefer AM, Alston CL, Blakely EL, Sharma S, Hughes I, Lim A, de Goede C, McEntagart M, Spinty S, Horrocks I, Roberts M, Woodward CE, Chinnery PF, Horvath R, Nesbitt V, Fratter C, Poulton J, Hanna MG, Pitceathly RDS, Taylor RW, Turnbull DM, McFarland R

Publication type: Article

Publication status: Published

Journal: Annals of Neurology

Year: 2019

Volume: 86

Issue: 2

Pages: 310-315

Print publication date: 01/08/2019

Online publication date: 11/06/2019

Acceptance date: 07/06/2019

Date deposited: 16/07/2019

ISSN (print): 0364-5134

ISSN (electronic): 1531-8249

Publisher: John Wiley and Sons Inc.


DOI: 10.1002/ana.25525

PubMed id: 31187502


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Funder referenceFunder name
203105/Z/16/ZWellcome Trust
C.L.A. was the recipient of an NIHR doctoral fellowship (NIHR‐HCS‐D12‐03‐04).
M.H.M. is funded by the Sigrid Jusélius Foundation.
Newcastle University Centre for Ageing and Vitality (supported by the Biotechnology and Biological Sciences Research Council and Medical Research Council [L016354])
P.F.C. is a Wellcome Trust Principal Research Fellow (212219/Z/18/Z), and a UK NIHR Senior Investigator
PFC: the Medical Research Council (UK) Centre for Translational Muscle Disease (G0601943), the Evelyn Trust,
PFC: receives support from the Medical Research Council Mitochondrial Biology Unit (MC_UP_1501/2),
R.D.S.P. is supported by a Medical Research Council Clinician Scientist Fellowship (MR/S002065/1).
R.H. is a Wellcome Investigator (109915/Z/15/Z), who receives support from the Wellcome Centre for Mitochondrial Research (203105/Z/16/Z),
RH: Medical Research Council (UK) (MR/N025431/1), the European Research Council (309548), the Wellcome Trust Pathfinder Scheme (201064/Z/16/Z), and the Newton Fund (UK/Turkey) (MR/N027302/1).
Y.S.N. holds an NIHR Clinical Lectureship in Neurology (CL‐2016‐01‐003) and was funded by the Medical Research Council Centre of Neuromuscular Diseases for his PhD study (MR/K000608/1).
UK National Institute for Health Research (NIHR) Biomedical Research Centre for Ageing and Age‐Related Disease award