title: A new disease-related mutation for mitochondrial encephalopathy lactic acidosis and strokelike episodes (MELAS) syndrome affects the ND4 subunit of the respiratory complex I.
abstract: The molecular lesions in two patients exhibiting classical clinical manifestations of MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) syndrome have been investigated. A recently reported disease-related A----G base substitution at nt 3243 of the mtDNA, in the DHU loop of tRNA(Leu), was detected by restriction-enzyme analysis of the relevant PCR-amplified segment of the mtDNA of one patient but was not observed, by either restriction-enzyme analysis or nucleotide sequencing, in the other. To define the molecular lesion in the patient who does not have the A----G base substitution at nt 3243, the total mitochondrial genome of the patient has been sequenced. An A----G base substitution at nt 11084, leading to a Thr-to-Ala amino acid replacement in the ND4 subunit of the respiratory complex I, is suggested to be a disease-related mutation.
authors.affiliation: Department of Biochemistry, Monash University, Clayton, Victoria, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Lertrit
authors.forename: A S
authors.initials: AS
authors.lastname: Noer
authors.forename: M J
authors.initials: MJ
authors.lastname: Jean-Francois
authors.forename: R
authors.initials: R
authors.lastname: Kapsa
authors.forename: X
authors.initials: X
authors.lastname: Dennett
authors.forename: D
authors.initials: D
authors.lastname: Thyagarajan
authors.forename: K
authors.initials: K
authors.lastname: Lethlean
authors.forename: E
authors.initials: E
authors.lastname: Byrne
authors.forename: S
authors.initials: S
authors.lastname: Marzuki
mesh_terms: D000140:Acidosis, Lactic / Q000201:enzymology / Q000235:genetics; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001927:Brain Diseases / Q000201:enzymology / Q000235:genetics*; D002561:Cerebrovascular Disorders / Q000201:enzymology / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry / Q000172:deficiency / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012356:RNA, Transfer, Leu / Q000235:genetics*; D015183:Restriction Mapping; D013577:Syndrome
chemical_list: D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu; D016660:NAD(P)H Dehydrogenase (Quinone); D003576:Electron Transport Complex IV