title: Identification of a novel mutation in the mtDNA ND5 gene associated with MELAS.
abstract: We report a novel G13513A mutation in the mitochondrial ND5 gene in a patient who had morphologically and biochemically abnormal muscle mitochondria and died at age 45 with a diagnosis of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). The mutation affects an evolutionarily conserved nucleotide and was heteroplasmic in muscle, leukocytes, and several autopsy tissues, including brain. The mutation was less abundant (<5%) in leukocytes from an asymptomatic sister and was not found in over 100 controls, thus satisfying accepted criteria for pathogenicity. Our report reinforces the concept of genetic heterogeneity in MELAS and confirms that MELAS can be due to mutations in polypeptide-coding mtDNA genes.
authors.affiliation: Department of Neurology, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: K
authors.initials: K
authors.lastname: Tanji
authors.forename: R
authors.initials: R
authors.lastname: Kulikova
authors.forename: S
authors.initials: S
authors.lastname: Shanske
authors.forename: L
authors.initials: L
authors.lastname: Vilarinho
authors.forename: A P
authors.initials: AP
authors.lastname: Hays
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000595:Amino Acid Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D004272:DNA, Mitochondrial