Novel mutations in COX15 in a long surviving Leigh syndrome patient with cytochrome c oxidase deficiency
- 1Department of Child Neurology, Istituto Nazionale Neurologico “C. Besta”, Milan, Italy
- 2Department of Molecular Neurogenetics, Istituto Nazionale Neurologico “C. Besta”, Milan, Italy
- 3Department of Neuroradiology, Istituto Nazionale Neurologico “C. Besta”, Milan, Italy
- Correspondence to: Massimo Zeviani Department of Molecular Neurogenetics, Istituto Nazionale Neurologico “C. Besta”, via Libero Temolo, 4 20126 Milano, Italy; zevianiistituto-besta.it
- Accepted 17 December 2004
- Revised 10 December 2004
Abstract
Background: Isolated cytochrome c oxidase (COX) deficiency is usually associated with mutations in several factors involved in the biogenesis of COX.
Methods: We describe a patient with atypical, long surviving Leigh syndrome carrying two novel mutations in the COX15 gene, which encodes an enzyme involved in the biosynthesis of heme A.
Results: Only two COX15 mutated patients, one with severe neonatal cardiomyopathy, the other with rapidly fatal Leigh syndrome, have been described to date. In contrast, our patient had a slowly progressive course with no heart involvement. COX deficiency was mild in muscle and a normal amount of fully assembled COX was present in cultured fibroblasts.
Conclusions: The clinical and biochemical phenotypes in COX15 defects are more heterogeneous than in other conditions associated with COX deficiency, such as mutations in SURF1.
- 2D-BNE, two dimensional Blue Native electrophoresis
- COX, cytochrome c oxidase
- mtDNA, mitochondrial DNA
Footnotes
-
This work was supported by Fondazione Telethon-Italy (grant no. GGP030039), Fondazione Pierfranco e Luisa Mariani, Ricerca Finalizzata Ministero della Salute FR-2002/158, Fondazione Cariplo, and a EUMITOCOMBAT network grant from the European Union Framework Program 6.
-
Competing interests: none declared
