The mitochondrial DNA G13513A transition in ND5 is associated with a LHON/MELAS overlap syndrome and may be a frequent cause of MELAS.
We report on 4 male patients with clinical, radiological, and muscle biopsy findings typical of the mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) phenotype. Skeletal muscle mitochondrial DNA (mtDNA) analysis showed that all patients harbored a heteroplasmic G13513A mutation in the ND5 subunit gene. One of these cases (Patient 1) presented with symptoms characteristic of Leber's hereditary optic neuropathy (LHON) 2 years before the first stroke-like episode. Quantitative analysis in several postmortem tissue sections showed that the relative proportions of mutant mtDNA were generally lower than those reported with other pathogenic mtDNA mutations. Single-fiber polymerase chain reaction studies demonstrated significantly higher amounts of mutant mtDNA in ragged red fibers (RRFs) compared with non-RRFs. This study indicates that the G13513A transition is likely to be pathogenic, that it can cause an LHON/MELAS overlap syndrome, and that it may be a more frequent cause of MELAS than previously recognized.
Pulkes
T
T
Department of Clinical Neurology, Institute of Neurology, Queen Square, London, England, UK.
Eunson
L
L
Patterson
V
V
Siddiqui
A
A
Wood
N W
NW
Nelson
I P
IP
Morgan-Hughes
J A
JA
Hanna
M G
MG
D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I; D003576:Electron Transport Complex IV / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics*; D008297:Male; D008931:Mitochondria, Muscle / Q000235:genetics / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics; D015418:Optic Atrophies, Hereditary / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction
D004272:DNA, Mitochondrial; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I