title: MELAS: clinical features, biochemistry, and molecular genetics.
abstract: We studied 23 patients with clinically defined mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), 25 oligosymptomatic or asymptomatic maternal relatives, and 50 mitochondrial disease control subjects for the presence of a previously reported heteroplasmic point mutation at nt 3,243 in the transfer RNA(Leu(UUR)) gene of mitochondrial DNA. We found a high concordance between clinical diagnosis of MELAS and transfer RNA(Leu(UUR)) mutation, which was present in 21 of the 23 patients with MELAS, all 11 oligosymptomatic and 12 of 14 asymptomatic relatives, but in only five of 50 patients without MELAS. The proportion of mutant genomes in muscle ranged from 56 to 95% and was significantly higher in the patients with MELAS than in their oligosymptomatic or asymptomatic relatives. In subjects in whom both muscle and blood were studied, the percentage of mutations was significantly lower in blood and was not detected in three of 12 asymptomatic relatives. The activities of complexes I + III, II + III, and IV were decreased in muscle biopsies harboring the mutation, but there was no clear correlation between percentage of mutant mitochondrial DNAs and severity of the biochemical defect.
authors.affiliation: H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Columbia-Presbyterian Medical Center, New York, NY.
authors.forename: E
authors.initials: E
authors.lastname: Ciafaloni
authors.forename: E
authors.initials: E
authors.lastname: Ricci
authors.forename: S
authors.initials: S
authors.lastname: Shanske
authors.forename: C T
authors.initials: CT
authors.lastname: Moraes
authors.forename: G
authors.initials: G
authors.lastname: Silvestri
authors.forename: M
authors.initials: M
authors.lastname: Hirano
authors.forename: S
authors.initials: S
authors.lastname: Simonetti
authors.forename: C
authors.initials: C
authors.lastname: Angelini
authors.forename: M A
authors.initials: MA
authors.lastname: Donati
authors.forename: C
authors.initials: C
authors.lastname: Garcia
mesh_terms: D000140:Acidosis, Lactic / Q000201:enzymology / Q000235:genetics*; D000328:Adult; D001927:Brain Diseases / Q000201:enzymology / Q000235:genetics*; D002561:Cerebrovascular Disorders / Q000201:enzymology / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000032:analysis; D006801:Humans; D008499:Medical Records; D008875:Middle Aged; D008928:Mitochondria / Q000648:ultrastructure*; D009035:Mothers; D009135:Muscular Diseases / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome
chemical_list: D004272:DNA, Mitochondrial