title: Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy.
abstract: Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as 'benign cytochrome c oxidase deficiency myopathy' is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T>C mt-tRNA(Glu) mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNA(Glu) may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.
authors.affiliation: Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. rita.horvath@ncl.ac.uk
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
authors.forename: John P
authors.initials: JP
authors.lastname: Kemp
authors.forename: Helen A L
authors.initials: HA
authors.lastname: Tuppen
authors.forename: Gavin
authors.initials: G
authors.lastname: Hudson
authors.forename: Anders
authors.initials: A
authors.lastname: Oldfors
authors.forename: Suely K N
authors.initials: SK
authors.lastname: Marie
authors.forename: Ali-Reza
authors.initials: AR
authors.lastname: Moslemi
authors.forename: Serenella
authors.initials: S
authors.lastname: Servidei
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Holme
authors.forename: Sara
authors.initials: S
authors.lastname: Shanske
authors.forename: Gittan
authors.initials: G
authors.lastname: Kollberg
authors.forename: Parul
authors.initials: P
authors.lastname: Jayakar
authors.forename: Angela
authors.initials: A
authors.lastname: Pyle
authors.forename: Harold M
authors.initials: HM
authors.lastname: Marks
authors.forename: Elke
authors.initials: E
authors.lastname: Holinski-Feder
authors.forename: Mena
authors.initials: M
authors.lastname: Scavina
authors.forename: Maggie C
authors.initials: MC
authors.lastname: Walter
authors.forename: Jorida
authors.initials: J
authors.lastname: Coku
authors.forename: Andrea
authors.initials: A
authors.lastname: Günther-Scholz
authors.forename: Paul M
authors.initials: PM
authors.lastname: Smith
authors.forename: Robert
authors.initials: R
authors.lastname: McFarland
authors.forename: Zofia M A
authors.initials: ZM
authors.lastname: Chrzanowska-Lightowlers
authors.forename: Robert N
authors.initials: RN
authors.lastname: Lightowlers
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: Mar
authors.initials: M
authors.lastname: Tulinius
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D001483:Base Sequence; D030401:Cytochrome-c Oxidase Deficiency / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D003937:Diagnosis, Differential; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008967:Molecular Biology; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000473:pathology; D009690:Nucleic Acid Conformation; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D011379:Prognosis