Leigh syndrome caused by mutations in MTFMT is associated with a better prognosis

H Hayhurst; IFM de Coo; D Piekutowska-Abramczuk; CL Alston; S Sharma; K Thompson; R Rius; L He; S Hopton; R Ploski; E Ciara; NJ Lake; AG Compton; MB Delatycki; A Verrips; PE Bonnen; SA Jones; AA Morris; D Shakespeare; J Christodoulou; D Wesol-Kucharska; D Rokicki; HJM Smeets; E Pronicka; DR Thorburn; GS Gorman; R McFarland; RW Taylor; YS Ng

Journal article

Leigh syndrome caused by mutations in MTFMT is associated with a better prognosis

H Hayhurst, IFM de Coo, D Piekutowska-Abramczuk, CL Alston, S Sharma, K Thompson, R Rius, L He, S Hopton, R Ploski, E Ciara, NJ Lake, AG Compton, MB Delatycki, A Verrips, PE Bonnen, SA Jones, AA Morris, D Shakespeare, J Christodoulou Show all

Annals of Clinical and Translational Neurology | WILEY | Published : 2019

DOI: 10.1002/acn3.725

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Abstract

Objectives: Mitochondrial methionyl-tRNA formyltransferase (MTFMT) is required for the initiation of translation and elongation of mitochondrial protein synthesis. Pathogenic variants in MTFMT have been associated with Leigh syndrome (LS) and mitochondrial multiple respiratory chain deficiencies. We sought to elucidate the spectrum of clinical, neuroradiological and molecular genetic findings of patients with bi-allelic pathogenic variants in MTFMT. Methods: Retrospective cohort study combining new cases and previously published cases. Results: Thirty-eight patients with pathogenic variants in MTFMT were identified, including eight new cases. The median age of presentation was 14 months (ran..

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University of Melbourne Researchers

Rocio Rius Author

Alison G Compton Author

Martin Delatycki Author

John Christodoulou Author

Grants

Awarded by Biotechnology and Biological Sciences Research Council

Funding Acknowledgements

The work in Newcastle was supported by the Wellcome Centre for Mitochondrial Research (203105/Z/16/Z), Newcastle University Centre for Ageing and Vitality (supported by the Biotechnology and Biological Sciences Research Council and Medical Research Council L016354), UK NIHR Biomedical Research Centre for Ageing and Age-related disease award to the Newcastle upon Tyne Hospitals NHS Foundation Trust, National Institute for Health Research (NIHR), the Lily Foundation and the UK NHS Specialist Commissioners which funds the "Rare Mitochondrial Disorders of Adults and Children" Diagnostic Service in Newcastle upon Tyne (http://www.newcastle-mitochond ria. com/). Y.S.N holds a NIHR Clinical Lectureship in Neurology (CL-2016-01-003) and was funded by the MRC Centre of Neuromuscular diseases for his PhD study (MR/K000608/1). C.L.A was the recipient of a National Institute for Health Research (NIHR) doctoral fellowship (NIHR-HCS-D12-03-04). We are extremely grateful to the members of the MRC Mitochondrial Disease Patient Cohort and staff of the NHS Highly Specialised Mitochondrial Disease Service laboratory in Newcastle. Additional research support was from grants and fellowships from the Australian National Health and Medical Research Council (GNT1068409, GNT1022896), the Victorian Government's Operational Infrastructure Support Program and the Crane and Perkins families. N.J.L. was the recipient of an Australian Postgraduate Award and an Australian Mitochondrial Disease Foundation scholarship. This work was supported by the Children's Memorial Health Institute grants: 238/16 (D.P-A) and S145/16 (E.P). H.J.M.S was supported by Princes Beatrix Spierfonds (W.OR11-24) and Stichting MetaKids grants. The views expressed are those of the authors and not necessarily of the NHS, NIHR, or Department of Health.