title: A novel mutation in the mitochondrial tRNA Asn gene associated with a lethal disease.
abstract: We describe a lethal mitochondrial disease in a 10-month-old child who presented with encephalomyopathy. Histochemical and electron microscopy examinations of skeletal muscle biopsy revealed abnormal mitochondria associated with a combined deficiency of complexes I and IV. After excluding mitochondrial DNA deletions and depletion, direct sequencing was used to screen for mutation in all transfer RNA (tRNA) genes. A T-to-C substitution at position 5693 in the tRNA(Asn) gene was found in blood and muscle. Microdissection of muscle biopsy and its analysis revealed the highest level of this mutation in cytochrome c oxidase (COX)-negative fibres. We suggest that this novel mutation would affect the anticodon loop structure of the tRNA(Asn) and cause a fatal mitochondrial disease.
authors.affiliation: Laboratoire de Biochimie A, Centre Hospitalier et Universitaire de Caen, Avenue Côte de Nacre, 14033 Caen cedex, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Coulbault
authors.forename: Danielle
authors.initials: D
authors.lastname: Herlicoviez
authors.forename: Françoise
authors.initials: F
authors.lastname: Chapon
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Read
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Penniello
authors.forename: Pascal
authors.initials: P
authors.lastname: Reynier
authors.forename: Guillemette
authors.initials: G
authors.lastname: Fayet
authors.forename: Anne
authors.initials: A
authors.lastname: Lombès
authors.forename: Philippe
authors.initials: P
authors.lastname: Jauzac
authors.forename: Stéphane
authors.initials: S
authors.lastname: Allouche
mesh_terms: D030401:Cytochrome-c Oxidase Deficiency / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D003576:Electron Transport Complex IV / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008931:Mitochondria, Muscle / Q000473:pathology*; D017237:Mitochondrial Encephalomyopathies / Q000150:complications / Q000209:etiology / Q000235:genetics / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology*; D009154:Mutation; D012348:RNA, Transfer, Asn / Q000235:genetics*
chemical_list: D012348:RNA, Transfer, Asn; D003576:Electron Transport Complex IV