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The mitochondrial DNA G13513A transition in ND5 is associated with a LHON/MELAS overlap syndrome and may be a frequent cause of MELAS
Author(s) -
Pulkes Teeratorn,
Eunson Louise,
Patterson Victor,
Siddiqui Asra,
Wood Nicholas W.,
Nelson Isabelle P.,
MorganHughes John A.,
Hanna Michael G.
Publication year - 1999
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(199912)46:6<916::aid-ana16>3.0.co;2-r
Subject(s) - heteroplasmy , mitochondrial encephalomyopathy , mitochondrial dna , melas syndrome , lactic acidosis , muscle biopsy , mitochondrial disease , mitochondrial myopathy , biology , mitochondrial encephalomyopathies , mutation , genetics , chronic progressive external ophthalmoplegia , pathology , gene , medicine , biopsy , endocrinology
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.