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dc.contributor.authorNg, Yi Shiau
dc.contributor.authorLax, Nichola Z
dc.contributor.authorMaddison, Paul
dc.contributor.authorAlston, Charlotte L
dc.contributor.authorBlakely, Emma L
dc.contributor.authorHepplewhite, Philippa D
dc.contributor.authorRiordan, Gillian
dc.contributor.authorMeldau, Surita
dc.contributor.authorChinnery, Patrick
dc.contributor.authorPierre, Germaine
dc.contributor.authorChronopoulou, Efstathia
dc.contributor.authorDu, Ailian
dc.contributor.authorHughes, Ieuan
dc.contributor.authorMorris, Andrew A
dc.contributor.authorKamakari, Smaragda
dc.contributor.authorChrousos, Georgia
dc.contributor.authorRodenburg, Richard J
dc.contributor.authorSaris, Christiaan GJ
dc.contributor.authorFeeney, Catherine
dc.contributor.authorHardy, Steven A
dc.contributor.authorSakakibara, Takafumi
dc.contributor.authorSudo, Akira
dc.contributor.authorOkazaki, Yasushi
dc.contributor.authorMurayama, Kei
dc.contributor.authorMundy, Helen
dc.contributor.authorHanna, Michael G
dc.contributor.authorOhtake, Akira
dc.contributor.authorSchaefer, Andrew M
dc.contributor.authorChampion, Mike P
dc.contributor.authorTurnbull, Doug M
dc.contributor.authorTaylor, Robert W
dc.contributor.authorPitceathly, Robert DS
dc.contributor.authorMcFarland, Robert
dc.contributor.authorGorman, Gráinne S
dc.date.accessioned2018-10-10T05:17:35Z
dc.date.available2018-10-10T05:17:35Z
dc.date.issued2018-04
dc.identifier.issn2352-3964
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/283380
dc.description.abstractMutations 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 10years (range: 5·4months-37years, IQR=17·9years). 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.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBrain
dc.subjectHumans
dc.subjectSyndrome
dc.subjectElectron Transport Complex I
dc.subjectMitochondrial Proteins
dc.subjectMagnetic Resonance Imaging
dc.subjectCohort Studies
dc.subjectMutation
dc.subjectAdolescent
dc.subjectAdult
dc.subjectChild
dc.subjectFemale
dc.subjectMale
dc.subjectYoung Adult
dc.titleMT-ND5 Mutation Exhibits Highly Variable Neurological Manifestations at Low Mutant Load.
dc.typeArticle
prism.endingPage93
prism.publicationDate2018
prism.publicationNameEBioMedicine
prism.startingPage86
prism.volume30
dc.identifier.doi10.17863/CAM.30748
dcterms.dateAccepted2018-02-12
rioxxterms.versionofrecord10.1016/j.ebiom.2018.02.010
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-04
dc.contributor.orcidChinnery, Patrick [0000-0002-7065-6617]
dc.identifier.eissn2352-3964
rioxxterms.typeJournal Article/Review
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (unknown)
pubs.funder-project-idWellcome Trust (101876/Z/13/Z)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (3819-1617-17)
pubs.funder-project-idDepartment of Health (via Newcastle University) (BH091682-RG81903)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International