Human Molecular Genetics, 2000, Vol. 9, No. 8 1245-1249
© 2000 Oxford University Press
A mutation in the human heme A:farnesyltransferase gene (COX10 ) causes cytochrome c oxidase deficiency
INSERM U393, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France, 1Department of Biological Sciences, Columbia University, New York, NY 10027, USA and 2Royal Free and University College Medical School, Department of Clinical Neurosciences, Rowland Hill Street, London NW3 2PF, UK
Cytochrome c oxidase (COX) defects are found in a clinically and genetically heterogeneous group of mitochondrial disorders. To date, mutations in only two nuclear genes causing COX deficiency have been described. We report here a genetic linkage study of a consanguineous family with an isolated COX defect and subsequent identification of a mutation in a third nuclear gene causing a deficiency of the enzyme. A genome-wide search for homozygosity allowed us to map the disease gene to chromosome 17p13.1–q11.1 (Zmax = 2.46; 
= 0.00 at the locus D17S799). This region encompasses two genes, SCO1 and COX10, encoding proteins involved in COX assembly. Mutation analysis followed by a complementation study in yeast permitted us to ascribe the COX deficiency to a homozygous missense mutation in the COX10 gene. This gene encodes heme A:farnesyltransferase, which catalyzes the first step in the conversion of protoheme to the heme A prosthetic groups of the enzyme. All three nuclear genes now linked to isolated COX deficiency are involved in the maturation and assembly of COX, emphasizing the major role of such genes in COX pathology.
+ To whom correspondence should be addressed. Tel: +33 1 47 38 15 84; Fax: +33 1 47 34 85 14; Email: roetig@necker.fr
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Trevisson, A. Burlina, M. Doimo, V. Pertegato, A. Casarin, L. Cesaro, P. Navas, G. Basso, G. Sartori, and L. Salviati Functional Complementation in Yeast Allows Molecular Characterization of Missense Argininosuccinate Lyase Mutations J. Biol. Chem., October 16, 2009; 284(42): 28926 - 28934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Leary, F. Sasarman, T. Nishimura, and E. A. Shoubridge Human SCO2 is required for the synthesis of CO II and as a thiol-disulphide oxidoreductase for SCO1 Hum. Mol. Genet., June 15, 2009; 18(12): 2230 - 2240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Wang, Y. Wang, and E. L. Hegg Regulation of the Heme A Biosynthetic Pathway: DIFFERENTIAL REGULATION OF HEME A SYNTHASE AND HEME O SYNTHASE IN SACCHAROMYCES CEREVISIAE J. Biol. Chem., January 9, 2009; 284(2): 839 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.M. Hall, R.J. Unwin, M.G. Hanna, and M.R. Duchen Renal function and mitochondrial cytopathy (MC): more questions than answers? QJM, October 1, 2008; 101(10): 755 - 766. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bastin, F. Aubey, A. Rotig, A. Munnich, and F. Djouadi Activation of Peroxisome Proliferator-Activated Receptor Pathway Stimulates the Mitochondrial Respiratory Chain and Can Correct Deficiencies in Patients' Cells Lacking Its Components J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1433 - 1441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Diaz, H. Fukui, S. Garcia, and C. T. Moraes Cytochrome C oxidase is required for the assembly/stability of respiratory complex I in mouse fibroblasts. Mol. Cell. Biol., July 1, 2006; 26(13): 4872 - 4881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Kaltimbacher, C. Bonnet, G. Lecoeuvre, V. Forster, J.-A. Sahel, and M. Corral-Debrinski mRNA localization to the mitochondrial surface allows the efficient translocation inside the organelle of a nuclear recoded ATP6 protein RNA, July 1, 2006; 12(7): 1408 - 1417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Cobine, F. Pierrel, S. C. Leary, F. Sasarman, Y.-C. Horng, E. A. Shoubridge, and D. R. Winge The P174L Mutation in Human Sco1 Severely Compromises Cox17-dependent Metallation but Does Not Impair Copper Binding J. Biol. Chem., May 5, 2006; 281(18): 12270 - 12276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Diaz, C. K. Thomas, S. Garcia, D. Hernandez, and C. T. Moraes Mice lacking COX10 in skeletal muscle recapitulate the phenotype of progressive mitochondrial myopathies associated with cytochrome c oxidase deficiency Hum. Mol. Genet., September 15, 2005; 14(18): 2737 - 2748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K.H. Tay, S. Sacconi, H. Ohran Akman, J. F. Morales, A. Morales, D. C. De Vivo, S. Shanske, E. Bonilla, and S. DiMauro Unusual Clinical Presentations in Four Cases of Leigh Disease, Cytochrome C Oxidase Deficiency, and SURF1 Gene Mutations J Child Neurol, August 1, 2005; 20(8): 670 - 674. [Abstract] [PDF]
|
|
|
|
 |
|
 S. K. H. Tay, C. Nesti, M. Mancuso, E. A. Schon, S. Shanske, E. Bonilla, M. M. Davidson, and S. DiMauro Studies of COX16, COX19, and PET191 in Human Cytochrome-c Oxidase Deficiency Arch Neurol, December 1, 2004; 61(12): 1935 - 1937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zeviani and S. Di Donato Mitochondrial disorders Brain, October 1, 2004; 127(10): 2153 - 2172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Leary, B. A. Kaufman, G. Pellecchia, G.-H. Guercin, A. Mattman, M. Jaksch, and E. A. Shoubridge Human SCO1 and SCO2 have independent, cooperative functions in copper delivery to cytochrome c oxidase Hum. Mol. Genet., September 1, 2004; 13(17): 1839 - 1848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C E Oquendo, H Antonicka, E A Shoubridge, W Reardon, and G K Brown Functional and genetic studies demonstrate that mutation in the COX15 gene can cause Leigh syndrome J. Med. Genet., July 1, 2004; 41(7): 540 - 544. [Full Text] [PDF]
|
|
|
|
|
|
S. K. H. Tay, S. Shanske, P. Kaplan, and S. DiMauro Association of Mutations in SCO2, a Cytochrome c Oxidase Assembly Gene, With Early Fetal Lethality Arch Neurol, June 1, 2004; 61(6): 950 - 952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Williams, I. Valnot, P. Rustin, and J.-W. Taanman Cytochrome c Oxidase Subassemblies in Fibroblast Cultures from Patients Carrying Mutations in COX10, SCO1, or SURF1 J. Biol. Chem., February 27, 2004; 279(9): 7462 - 7469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rotig and A. Munnich Genetic Features of Mitochondrial Respiratory Chain Disorders J. Am. Soc. Nephrol., December 1, 2003; 14(12): 2995 - 3007. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Antonicka, S. C. Leary, G.-H. Guercin, J. N. Agar, R. Horvath, N. G. Kennaway, C. O. Harding, M. Jaksch, and E. A. Shoubridge Mutations in COX10 result in a defect in mitochondrial heme A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated COX deficiency Hum. Mol. Genet., October 16, 2003; 12(20): 2693 - 2702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Fosslien Mitochondrial Medicine - Cardiomyopathy Caused by Defective Oxidative Phosphorylation Ann. Clin. Lab. Sci., October 1, 2003; 33(4): 371 - 395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. Carlson, A. Barrientos, A. Tzagoloff, and D. M. Glerum COX16 Encodes a Novel Protein Required for the Assembly of Cytochrome Oxidase in Saccharomyces cerevisiae J. Biol. Chem., January 31, 2003; 278(6): 3770 - 3775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. de Lonlay, C. Mugnier, D. Sanlaville, K. Chantrel-Groussard, P. Benit, S. Lebon, D. Chretien, N. Kadhom, S. Saker, G. Gyapay, et al. Cell complementation using Genebridge 4 human:rodent hybrids for physical mapping of novel mitochondrial respiratory chain deficiency genes Hum. Mol. Genet., December 15, 2002; 11(26): 3273 - 3281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Salviati, S. Sacconi, M. M. Rasalan, D. F. Kronn, A. Braun, P. Canoll, M. Davidson, S. Shanske, E. Bonilla, A. P. Hays, et al. Cytochrome c Oxidase Deficiency Due to a Novel SCO2 Mutation Mimics Werdnig-Hoffmann Disease Arch Neurol, May 1, 2002; 59(5): 862 - 865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Leary, B. C. Hill, C. N. Lyons, C. G. Carlson, D. Michaud, C. S. Kraft, K. Ko, D. M. Glerum, and C. D. Moyes Chronic Treatment with Azide in Situ Leads to an Irreversible Loss of Cytochrome c Oxidase Activity via Holoenzyme Dissociation J. Biol. Chem., March 22, 2002; 277(13): 11321 - 11328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A H V Schapira The "new" mitochondrial disorders J. Neurol. Neurosurg. Psychiatry, February 1, 2002; 72(2): 144 - 149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D'Aurelio, F. Pallotti, A. Barrientos, C. D. Gajewski, J. Q. Kwong, C. Bruno, M. F. Beal, and G. Manfredi In Vivo Regulation of Oxidative Phosphorylation in Cells Harboring a Stop-codon Mutation in Mitochondrial DNA-encoded Cytochrome c Oxidase Subunit I J. Biol. Chem., December 7, 2001; 276(50): 46925 - 46932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jaksch, C. Paret, R. Stucka, N. Horn, J. Muller-Hocker, R. Horvath, N. Trepesch, G. Stecker, P. Freisinger, C. Thirion, et al. Cytochrome c oxidase deficiency due to mutations in SCO2, encoding a mitochondrial copper-binding protein, is rescued by copper in human myoblasts Hum. Mol. Genet., December 1, 2001; 10(26): 3025 - 3035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Jaksch, R. Horvath, N. Horn, D. P. Auer, C. Macmillan, J. Peters, K.-D. Gerbitz, I. Kraegeloh-Mann, A. Muntau, V. Karcagi, et al. Homozygosity (E140K) in SCO2 causes delayed infantile onset of cardiomyopathy and neuropathy Neurology, October 23, 2001; 57(8): 1440 - 1446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Shoubridge Nuclear genetic defects of oxidative phosphorylation Hum. Mol. Genet., October 1, 2001; 10(20): 2277 - 2284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jaksch, S. Kleinle, C. Scharfe, T. Klopstock, D. Pongratz, J. Muller-Hocker, K.-D Gerbitz, S. Liechti-Gallati, H. Lochmuller, and R. Horvath Frequency of mitochondrial transfer RNA mutations and deletions in 225 patients presenting with respiratory chain deficiencies J. Med. Genet., October 1, 2001; 38(10): 665 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Ellison, J. Lofing, and G. A. Bitter Functional analysis of human MLH1 and MSH2 missense variants and hybrid human-yeast MLH1 proteins in Saccharomyces cerevisiae Hum. Mol. Genet., September 1, 2001; 10(18): 1889 - 1900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Geromel, N. Kadhom, I. Cebalos-Picot, O. Ouari, A. Polidori, A. Munnich, A. Rotig, and P. Rustin Superoxide-induced massive apoptosis in cultured skin fibroblasts harboring the neurogenic ataxia retinitis pigmentosa (NARP) mutation in the ATPase-6 gene of the mitochondrial DNA Hum. Mol. Genet., May 1, 2001; 10(11): 1221 - 1228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. VON KLEIST-RETZOW, J. YAO, J.-W. TAANMAN, K. CHANTREL, D. CHRETIEN, V. CORMIER-DAIRE, A. RÖTIG, A. MUNNICH, P. RUSTIN, and E. A SHOUBRIDGE Mutations in SURF1 are not specifically associated with Leigh syndrome J. Med. Genet., February 1, 2001; 38(2): 109 - 113. [Full Text]
|
|
|
|
|
|
V. Tiranti, P. Corona, M. Greco, J.-W. Taanman, F. Carrara, E. Lamantea, L. Nijtmans, G. Uziel, and M. Zeviani A novel frameshift mutation of the mtDNA COIII gene leads to impaired assembly of cytochrome c oxidase in a patient affected by Leigh-like syndrome Hum. Mol. Genet., November 1, 2000; 9(18): 2733 - 2742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Hanson, R. Carrozzo, F. Piemonte, A. Tessa, B. H. Robinson, and R. A. Capaldi Cytochrome c Oxidase-deficient Patients Have Distinct Subunit Assembly Profiles J. Biol. Chem., May 4, 2001; 276(19): 16296 - 16301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Hiser and J. P. Hosler Heme A Is Not Essential for Assembly of the Subunits of Cytochrome c Oxidase of Rhodobacter sphaeroides J. Biol. Chem., November 21, 2001; 276(48): 45403 - 45407. [Abstract] [Full Text] [PDF]
|
|