LHON/MELAS overlap syndrome associated with a mitochondrial MTND1 gene mutation.
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.
Blakely
Emma L
EL
Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, UK.
de Silva
Rajith
R
King
Andrew
A
Schwarzer
Verena
V
Harrower
Tim
T
Dawidek
Gervase
G
Turnbull
Douglass M
DM
Taylor
Robert W
RW
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
D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human