A novel mutation in the mitochondrial tRNA Asn gene associated with a lethal disease.
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.
Coulbault
Laurent
L
Laboratoire de Biochimie A, Centre Hospitalier et Universitaire de Caen, Avenue Côte de Nacre, 14033 Caen cedex, France.
Herlicoviez
Danielle
D
Chapon
Françoise
F
Read
Marie-Hélène
MH
Penniello
Marie-José
MJ
Reynier
Pascal
P
Fayet
Guillemette
G
Lombès
Anne
A
Jauzac
Philippe
P
Allouche
Stéphane
S
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*
D012348:RNA, Transfer, Asn; D003576:Electron Transport Complex IV