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: Laurent Coulbault, Danielle Herlicoviez, Françoise Chapon, Marie-Hélène Read, Marie-José Penniello, Pascal Reynier, Guillemette Fayet, Anne Lombès, Philippe Jauzac, Stéphane Allouche
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 329 Issue 3 Pg. 1152-4 (Apr 15 2005) ISSN: 0006-291X [Print] United States
• PMID: 15752774 (Publication Type: Case Reports, Journal Article)

Chemical References

• RNA, Transfer, Asn
• Electron Transport Complex IV

Topics

• Cytochrome-c Oxidase Deficiency (complications, genetics, pathology)
• Electron Transport Complex IV (genetics)
• Genetic Predisposition to Disease (genetics)
• Humans
• Infant
• Male
• Mitochondria, Muscle (pathology)
• Mitochondrial Encephalomyopathies (complications, etiology, genetics, pathology)
• Muscle, Skeletal (pathology)
• Mutation
• RNA, Transfer, Asn (genetics)