title: Severe lactic acidosis caused by a novel frame-shift mutation in mitochondrial-encoded cytochrome c oxidase subunit II.
abstract: We report the first frame-shift truncation mutation in a mitochondrial DNA (mtDNA)-encoded subunit II of cytochrome c oxidase (COXII). The mutation was identified by temporal temperature gradient gel electrophoresis (TTGE) followed by direct DNA sequencing in an infant who died at 12 days of age following a course of apnea, bradycardia, and severe lactic acidosis. The patient had a twin brother who died at two days of age of similar course. The mutation, 8042delAT, produced a truncated protein that was 72 amino acids shorter than the wild type protein. The mutant protein, missing one third of the amino acid residues at the C-terminal essential for hydrophilic interaction with cytochrome c, ligand binding to CuA and Mg, and the formation of proton and water channels, apparently has devastating effects on mitochondrial respiratory function.
authors.affiliation: Institute for Molecular and Human Genetics, Georgetown University Medical Center, Washington, DC 2007, USA. wonglj@gunet.georgetown.edu
authors.forename: L J
authors.initials: LJ
authors.lastname: Wong
authors.forename: P
authors.initials: P
authors.lastname: Dai
authors.forename: D
authors.initials: D
authors.lastname: Tan
authors.forename: M
authors.initials: M
authors.lastname: Lipson
authors.forename: A
authors.initials: A
authors.lastname: Grix
authors.forename: M
authors.initials: M
authors.lastname: Sifry-Platt
authors.forename: A
authors.initials: A
authors.lastname: Gropman
authors.forename: T J
authors.initials: TJ
authors.lastname: Chen
mesh_terms: D000140:Acidosis, Lactic / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics*; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D010375:Pedigree
chemical_list: D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV