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We sought to elucidate the spectrum of clinical, neuroradiological and molecular genetic findings of patients with bi\u2010allelic pathogenic variants in <jats:italic><jats:styled-content style=\"fixed-case\">MTFMT<\/jats:styled-content><\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Retrospective cohort study combining new cases and previously published cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010eight patients with pathogenic variants in <jats:italic><jats:styled-content style=\"fixed-case\">MTFMT<\/jats:styled-content><\/jats:italic> were identified, including eight new cases. The median age of presentation was 14\u00a0months (range: birth to 17\u00a0years, interquartile range [<jats:styled-content style=\"fixed-case\">IQR<\/jats:styled-content>] 4.5\u00a0years), with developmental delay and motor symptoms being the most frequent initial manifestation. Twenty\u2010nine percent of the patients survived into adulthood. <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> headings in <jats:italic><jats:styled-content style=\"fixed-case\">MTFMT<\/jats:styled-content><\/jats:italic> pathogenic variants included symmetrical basal ganglia changes (62%), periventricular and subcortical white matter abnormalities (55%), and brainstem lesions (48%). Isolated complex I and combined respiratory chain deficiencies were identified in 31% and 59% of the cases, respectively. Reduction of the mitochondrial complex I and complex <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> subunits was identified in the fibroblasts (13\/13). Sixteen pathogenic variants were identified, of which c.626C&gt;T was the most common. Seventy\u2010four percent of the patients were alive at their last clinical review (median 6.8\u00a0years, range: 14\u00a0months to 31\u00a0years, <jats:styled-content style=\"fixed-case\">IQR<\/jats:styled-content> 14.5\u00a0years).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Patients that harbour pathogenic variants in <jats:italic><jats:styled-content style=\"fixed-case\">MTFMT<\/jats:styled-content><\/jats:italic> have a milder clinical phenotype and disease progression compared to <jats:styled-content style=\"fixed-case\">LS<\/jats:styled-content> caused by other nuclear defects. Fibroblasts may preclude the need for muscle biopsy, to prove causality of any novel variant.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.725","type":"journal-article","created":{"date-parts":[[2019,2,18]],"date-time":"2019-02-18T01:46:43Z","timestamp":1550454403000},"page":"515-524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Leigh syndrome caused by mutations in <i><scp>MTFMT<\/scp><\/i> is associated with a better prognosis"],"prefix":"10.1002","volume":"6","author":[{"given":"Hannah","family":"Hayhurst","sequence":"first","affiliation":[{"name":"Wellcome Centre for Mitochondrial Research Institute of Neuroscience Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0533-7422","authenticated-orcid":false,"given":"Irenaeus F. 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