title: LHON/MELAS overlap syndrome associated with a mitochondrial MTND1 gene mutation.
abstract: Pathogenic point mutations in the mitochondrial MTND1 gene have previously been described in association with two distinct clinical phenotypes -- Leber hereditary optic neuropathy (LHON) and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Here we report the first heteroplasmic mitochondrial DNA (mtDNA) point mutation (3376G>A) in the MTND1 gene associated with an overlap syndrome comprising the clinical features of both LHON and MELAS. Muscle histochemistry revealed subtle mitochondrial abnormalities, while biochemical analysis showed an isolated complex I deficiency. Our findings serve to highlight the growing importance of mutations in mitochondrial complex I structural genes in MELAS and its associated overlap syndromes.
authors.affiliation: Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Blakely
authors.forename: Rajith
authors.initials: R
authors.lastname: de Silva
authors.forename: Andrew
authors.initials: A
authors.lastname: King
authors.forename: Verena
authors.initials: V
authors.lastname: Schwarzer
authors.forename: Tim
authors.initials: T
authors.lastname: Harrower
authors.forename: Gervase
authors.initials: G
authors.lastname: Dawidek
authors.forename: Douglass M
authors.initials: DM
authors.lastname: Turnbull
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
mesh_terms: D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000378:metabolism; D005260:Female; D006801:Humans; D017241:MELAS Syndrome / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D017354:Point Mutation
chemical_list: D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human