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 G1...

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Bibliographic Details
Published in:Annals of neurology 1999-12, Vol.46 (6), p.916-919
Main Authors: Pulkes, Teeratorn, Eunson, Louise, Patterson, Victor, Siddiqui, Asra, Wood, Nicholas W., Nelson, Isabelle P., Morgan-Hughes, John A., Hanna, Michael G.
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Diseases of striated muscles. Neuromuscular diseases
DNA, Mitochondrial - genetics
Electron Transport Complex I
Electron Transport Complex IV - genetics
Female
Genetic Predisposition to Disease
Humans
Male
Medical sciences
MELAS Syndrome - genetics
Mitochondria, Muscle - genetics
Mitochondria, Muscle - pathology
Muscle, Skeletal - pathology
NADH, NADPH Oxidoreductases - genetics
Neurology
Optic Atrophies, Hereditary - genetics
Point Mutation
Polymerase Chain Reaction
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Summary: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.
ISSN:0364-5134
1531-8249
DOI:10.1002/1531-8249(199912)46:6<916::AID-ANA16>3.0.CO;2-R