Approaches to finding the molecular basis of mitochondrial oxidative phosphorylation disorders

Twin Research and Human Genetics

Volumn 11, Issue 4, 2008, Pages 395-411

  Kirby, Denise M ^a   Thorburn, David R ^a,b  

^a ROYAL CHILDREN'S HOSPITAL   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Genes; Mitochondrial disease; OXPHOS; Respiratory chain

Indexed keywords

CARRIER PROTEIN; CELL NUCLEUS DNA; COMPLEX V; CYTOCHROME C OXIDASE; DEOXYRIBONUCLEOPROTEIN; MEMBRANE PROTEIN; MITOCHONDRIAL DNA; NUCLEAR PROTEIN; OXIDOREDUCTASE; PROTEIN CABC1; PROTEIN COQ2; PROTEIN MTND1; PROTEIN MTND2; PROTEIN MTND3; PROTEIN MTND4; PROTEIN NDUFA1; PROTEIN NDUFA11; PROTEIN NDUFS1; PROTEIN NDUFV1; PROTEIN NDUFV2; PROTEIN PDSS1; PROTEIN PDSS2; PROTEIN RRM2B; PROTEIN SLC25A3; PROTEIN TK2; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); SUCCINATE DEHYDROGENASE (UBIQUINONE); TRANSFER RNA; UBIQUINOL CYTOCHROME C REDUCTASE;

COMPLEX I DEFICIENCY; COMPLEX II DEFICIENCY; COMPLEX III DEFICIENCY; COMPLEX V DEFICIENCY; CYTOCHROME C OXIDASE DEFICIENCY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; ENZYME DEFICIENCY; FAMILY HISTORY; GENE DELETION; GENE FUNCTION; GENE MUTATION; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC RISK; HISTOCHEMISTRY; HUMAN; MITOCHONDRIAL OXIDATIVE PHOSPHORYLATION DISORDER; MUSCLE BIOPSY; NEUROIMAGING; NEUROPATHOLOGY; PHENOTYPE; PRIORITY JOURNAL; REVIEW; RISK FACTOR; X CHROMOSOME;

DNA, MITOCHONDRIAL; ELECTRON TRANSPORT CHAIN COMPLEX PROTEINS; FEMALE; HUMANS; MALE; METABOLISM, INBORN ERRORS; MITOCHONDRIAL DISEASES; MUTATION; OXIDATIVE PHOSPHORYLATION; PEDIGREE; PHENOTYPE;

EID: 49749141079     PISSN: 18324274     EISSN: None     Source Type: Journal    
DOI: 10.1375/twin.11.4.395     Document Type: Review

References (103)

1. Alexander, C., Votruba, M., Pesch, U. E., Thiselton, D. L., Mayer, S., Moore, A., Rodriguez, M., Kellner, U., Leo-Kottler, B., Auburger, G., Bhattacharya, S. S., & Wissinger, B. (2000). OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nature Genetics, 26, 211-215.
2. Allikmets, R., Raskind, W. H., Hutchinson, A., Schueck, N. D., Dean, M., & Koeller, D. M. (1999). Mutation of a putative mitochondrial iron transporter gene (ABC7) in X- linked sideroblastic anemia and ataxia (XLSA/A). Human Molecular Genetics, 8, 743-749.
3. Antonicka, H., Mattman, A., Carlson, C. G., Glerum, D. M., Hoffbuhr, K. C., Leary, S. C., Kennaway, N. G., & Shoubridge, E. A. (2003). Mutations in COX15 Produce a Defect in the Mitochondrial Heme Biosynthetic Pathway, Causing Early-Onset Fatal Hypertrophic Cardiomyopathy. American Journal of Human Genetics, 72, 101-114.
4. Bender, A., Krishnan, K. J., Morris, C. M., Taylor, G. A., Reeve, A. K., Perry, R. H., Jaros, E., Hersheson, J. S., Betts, J., Klopstock, T., Taylor, R. W., & Turnbull, D. M. (2006). High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nature Genetics, 38, 515-517.
5. Benit, P., Beugnot, R., Chretien, D., Giurgea, I., De Lonlay-Debeney, P., Issartel, J. P., Corral-Debrinski, M., Kerscher, S., Rustin, P., Rotig, A., & Munnich, A. (2003). Mutant NDUFV2 subunit of mitochondrial complex I causes early onset hypertrophic cardiomyopathy and encephalopathy. Human Mutation, 21, 582-586.
6. Benit, P., Chretien, D., Kadhom, N., de Lonlay-Debeney, P., Cormier-Daire, V., Cabral, A., Peudenier, S., Rustin, P., Munnich, A., & Rotig, A. (2001). Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex 1 deficiency. American Journal of Human Genetics, 68, 1344-1352.
7. Benit, P., Slama, A., Cartault, F., Giurgea, I., Chretien, D., Lebon, S., Marsac, C., Munnich, A., Rotig, A., & Rustin, P. (2004). Mutant NDUFS3 subunit of mitochondrial Complex I causes Leigh syndrome. Journal of Medical Genetics, 41, 14-17.
8. Berger, I., Hershkovitz, E., Shaag, A., Edvardson, S., Saada, A., & Elpeleg, O. (2008). Mitochondrial complex I deficiency caused by a deleterious NDUFA11 mutation. Annals of Neurology, 63, 405-408.
9. Bertini, I., & Rosato, A. (2008). Menkes disease. Cellular and Molecular Life Sciences, 65, 89-91.
10. Bione, S., Dadamo, P., Maestrini, E., Gedeon, A. K., Bolhuis, P. A., & Toniolo, D. (1996). A novel X-linked gene, G4.5. is responsible for Barth syndrome. Nature Genetics, 12, 385-389.
11. Bohm, M., Pronicka, E., Karczmarewicz, E., Pronicki, M., Piekutowska-Abramczuk, D., Sykut-Cegielska, J., Mierzewska, H., Hansikova, H., Vesela, K., Tesarova, M., Houstkova, H., Houstek, J., & Zeman, J. (2006). Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency. Pediatric Research, 59, 21-26.
12. Bourdon, A., Minai, L., Serre, V., Jais, J. P., Sarzi, E., Aubert, S., Chretien, D., de Lonlay, P., Paquis-Flucklinger, V., Arakawa, H., Nakamura, Y., Munnich, A., & Rotig, A. (2007). Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. Nature Genetics, 39, 776-780.
13. Bourgeron, T., Rustin, P., Chretien, D., Birch-Machin, M., Bourgeois, M., Viegas-Pequignot, E., Munnich, A., & Rotig, A. (1995). Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nature Genetics, 11, 144-149.
14. Bykhovskaya, Y., Casas, K., Mengesha, E., Inbal, A., & Fischel-Ghodsian, N. (2004). Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA). American Journal of Human Genetics, 74, 1303-1308.
15. Carrozzo, R., Dionisi-Vici, C., Steuerwald, U., Lucioli, S., Deodato, F., Di Giandomenico, S., Bertini, E., Franke, B., Kluijtmans, L. A., Meschini, M. C., Rizzo, C., Piemonte, F., Rodenburg, R., Santer, R., Santorelli, F. van Rooij, A., Vermunt-de Koning, D., Morava, E., & Wevers, R. A. (2007). SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness. Brain: A Journal of Neurology, 130, 862-874.
16. Casari, G., De Fusco, M., Ciarmatori, S., Zeviani, M., Mora, M., Fernandez, P., De Michele, G., Filla, A., Cocozza, S., Marconi, R., Durr, A., Fontaine, B., & Ballabio, A. (1998). Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell, 93, 973-983.
17. Coenen, M. J., Antonicka, H., Ugalde, C., Sasarman, F., Rossi, R., Heister, J. G., Newbold, R. F., Trijbels, F. J., van den Heuvel, L. P., Shoubridge, E. A., & Smeitink, J. A. (2004) Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency. New England Journal of Medicine, 351, 2080-2086.
18. Davey, K. M., Parboosingh, J. S., McLeod, D. R., Chan, A., Casey, R., Ferreira, P., Snyder, F. F, Bridge, P. J., & Bernier, F. P. (2006). Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition. Journal of Medical Genetics, 43, 385-393.
19. de Lonlay, P., Valnot, I., Barrientos, A., Gorbatyuk, M., Tzagoloff, A., Taanman, J. W., Benayoun, E., Chretien, D., Kadhom, N., Lombes, A., de Baulny, H. O., Niaudet, P., Munnich, A., Rustin, P., & Rotig, A. (2001). A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure. Nature Genetics, 29, 57-60.
20. De Meirleir, L., Seneca, S. H., Lissens, W., De Clercq, I., Eyskens, F., Gerlo, E., Smet, J., & Van Coster, R. (2004). Complex V deficiency due to a mutation in the assembly gene ATP12. Journal of Medical Genetics, 41, 120-124.
21. Delettre, C., Lenaers, G., Griffoin, J. M., Gigarel, N., Lorenzo, C., Belenguer, P., Pelloquin, L., Grosgeorge, J., Turc-Carel, C., Perret, E., Astarie-Dequeker, C., Lasquellec, L., Arnaud, B., Ducommun, B., Kaplan, J., & Hamel, C. P. (2000). Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nature Genetics, 26, 207-210.
22. DiMauro, S., & Schon, E. A. (2003). Mitochondrial respiratory-chain diseases. New England Journal of Medicine, 348, 2656-2668.
23. DiMauro, S., & Schon, E. A. (2008). Mitochondrial disorders in the nervous system. Annual Review of Neuroscience.
24. Dunning, C. J., McKenzie, M., Sugiana, C., Lazarou, M., Silke, J., Connelly, A., Fletcher, J. M., Kirby, D..M., Thorburn, D. R., & Ryan, M. T. (2007). Human CIA30 is involved in the early assembly of mitochondrial complex I and mutations in its gene cause disease. EMBO Journal, 26, 3227-3237.
25. Edvardson, S., Shaag, A., Kolesnikova, O., Gomori, J. M., Tarassov, I., Einbinder, I., Saada, A., & Elpeleg, O. (2007). Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia. American Journal of Human Genetics, 81, 857-862.
26. Fernandez-Moreira, D., Ugalde, C., Smeets, R., Rodenburg, R. J., Lopez-Laso, E., Ruiz-Falco, M. L., Briones, P., Martin, M. A., Smeitink, J. A., & Arenas, J. (2007). X-linked NDUFA1 gene mutations associated with mitochondrial encephalomyopathy. Annals of Neurology, 61, 73-83.
27. Hakonen, A., Davidzon, G., Salemi, R., Bindoff, L., Van Goethem, G., Di Mauro, S., Thorburn, D. R. & Suomalainen, A. (2006) Abundance of the POLG disease mutations in Europe, Australia, New Zealand, and the United States explained by single ancient European founders. European Journal of Human Genetics, 15, 779-783.
28. Hakonen, A. H., Isohanni, P., Paetau, A., Herva, R., Suomalainen, A., & Lonnqvist, T. (2007). Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion. Brain: A Journal of Neurology, 130, 3032-3040.
29. Hansen, J.J., Durr, A., Cournu-Rebeix, I., Georgopoulos, C., Ang, D., Nielsen, M. N., Davoine, C. S., Brice, A., Fontaine, B., Gregersen, N., & Bross, P. (2002). Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. American Journal of Human Genetics, 70, 1328-1332.
30. Haut, S., Brivet, M., Touati, G., Rustin, P., Lebon, S., Garcia-Cazorla, A., Saudubray, J. M., Boutron, A., Legrand, A., & Slama, A. (2003). A deletion in the human QP-C gene causes a complex III deficiency resulting in hypoglycaemia and lactic acidosis. Human Genetics, 113, 118-122.
31. Hinson, J. T., Fantin, V. R., Schonberger, J., Breivik, N., Siem, G., McDonough, B., Sharma, P., Keogh, I., Godinho, R., Santos, F., Esparza, A., Nicolau, Y., Selvaag, E., Cohen, B. H., Hoppel, C. L., Tranebjaerg, L., Eavey, R. D., Seidman, J. G., & Seidman, C. E. (2007). Missense mutations in the BCS1L gene as a cause of the Bjornstad syndrome. New England Journal of Medicine, 356, 809-819.
32. Holt, I. J., Harding, A. E., & Morgan-Hughes, J. A. (1988). Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature, 331, 717-719.
33. Hudson, G., Amati-Bonneau, P., Blakely, E. L., Stewart, J. D., He, L., Schaefer, A. M., Griffiths, P. G., Ahlqvist, K., Suomalainen, A., Reynier, P., McFarland, R., Turnbull, D. M., Chinnery, P. F., & Taylor, R. W. (2008). Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: A novel disorder of mtDNA maintenance. Brain: A Journal of Neurology, 131, 329-337.
34. Hudson, G., & Chinnery, P. F. (2006). Mitochondrial DNA polymerase-γ and human disease. Human Molecular Genetics, 15, R244-R252.
35. Kaukonen, J., Juselius, J. K., Tiranti, V., Kyttala, A., Zeviani, M., Comi, G. P., Keranen, S., Peltonen, L., & Suomalainen, A. (2000). Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science, 289, 782-785.
36. Kirby, D. M., Crawford, M., Cleary, M. A., Dahl, H. H. M., Dennett, X., & Thorburn, D. R. (1999). Respiratory chain complex I deficiency. An underdiagnosed energy generation disorder. Neurology, 52, 1255-1264.
37. Kirby, D. M., Kahler, S. G., Freckmann, M. L., Reddihough, D., & Thorburn, D. R. (2000). Leigh disease caused by the mitochondrial DNA G14459A mutation in two unrelated families. Annals of Neurology, 48, 102-104.
38. Kirby, D. M., Salemi, R., Sugiana, C., Ohtake, A., Parry, L., Bell, K. M., Kirk, E., Boneh, A., Taylor, R. W., Dahl, H. H. M., Ryan, M. T., & Thorburn, D. R. (2004). NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency. Journal of Clinical Investigation, 114, 837-845.
39. Koehler, C. M., Leuenberger, D., Merchant, S., Renold, A., Junne, T., & Schatz, G. (1999). Human deafness dystonia syndrome is a mitochondrial disease. Proceedings of the National Academy of Sciences of the United States of America, 96, 2141-2146.
40. Lagier-Tourenne, C., Tazir, M., Lopez, L. C., Quinzii, C. M., Assoum, M., Drouot, N., Busso, C., Makri, S., Ali-Pacha, L., Benhassine, T., Anheim, M., Lynch, D. R., Thibault, C., Plewniak, F., Bianchetti, L., Tranchant, C., Poch, O., DiMauro, S., Mandel, J. L., Barros, M. H., Hirano, M., & Koenig, M. (2008). ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency. American Journal of Human Genetics, 82, 661-672.
41. Lebon, S., Chol, M., Benit, P., Mugnier, C., Chretien, D., Giurgea, I., Kern, I., Girardin, E., Hertz-Pannier, L., de Lonlay, P., Rötig, A., Rustin, P., & Munnich, A. (2003). Recurrent de novo mitochondrial DNA mutations in respiratory chain deficiency. Journal of Medical Genetics, 40, 896-899.
42. Loeffen, J., Elpeleg, O., Smeitink, J., Smeets, R., Stockler-Ipsiroglu, S., Mandel, H., Sengers, R., Trijbels, F., & van den Heuvel, L. (2001). Mutations in the complex I NDUFS2 gene of patients with cardiomyopathy and encephalomyopathy. Annals of Neurology, 49, 195-201.
43. Loeffen, J., Smeitink, J., Triepels, R., Smeets, R., Schuelke, M., Sengers, R., Trijbels, F., Hamel, B., Mullaart, R., & van den Heuvel, L. (1998). The first nuclear-encoded complex I mutation in a patient with Leigh syndrome. American Journal of Human Genetics, 63, 1598-1608.
44. Longley, M., Clark, S., Yu Wai Man, C., Hudson, G., Durham S.E., Taylor R. W, Nightingale, S., Turnbull, D. M., Copeland, W. C., & Chinnery, P. F. (2006) Mutant POLG2 disrupts DNA polymerase γ subunits and causes progressive external ophthalmoplegia. American Journal of Human Genetics, 78, 1026-1034.
45. López, L. C., Schuelke, M., Quinzii, C. M., Kanki, T., Rodenburg, R. J. T., Naini, A., DiMauro, S., & Hirano, M. (2006). Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) Mutations. American Journal of Human Genetics, 79, 1125-1129.
46. Mandei, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S., Cohen, N. (2001). The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Nature Genetics, 29, 337-341.
47. Mayr, J. A., Merkel, O., Kohlwein, S. D., Gebhardt, B. R., Bohles, H., Fotschl, U., Koch, J., Jaksch, M., Lochmuller, H., Horvath, R., Freisinger, P., & Sperl, W. (2007). Mitochondrial phosphate-carrier deficiency: A novel disorder of oxidative phosphorylation. American Journal of Human Genetics, 80, 478-484.
48. McFarland, R., Elson, J. L., Taylor, R. W., Howell, N., Turnbull, D. M. (2004). Assigning pathogenicity to mitochondrial tRNA mutations: When 'definitely maybe' is not good enough. Trends in Genetics, 20, 591-596.
49. McKenzie, M., Lazarou, M., Thorburn, D. R., & Ryan, M. T. (2006). Mitochondrial respiratory chain super-complexes are destabilized in Barth syndrome patients. Journal of Molecular Biology, 361, 462-469.
50. Miller, C., Saada, A., Shaul, N., Shabtai, N., Ben-Shalom, E., Shaag, A., Hershkovitz, E., & Elpeleg, O. (2004). Defective mitochondrial translation caused by a ribosomal protein (MRPS16) mutation. Annals of Neurology, 56, 734-738.
51. Mitchell, A. L., Elson, J. L., Howell, N., Taylor, R. W., Turnbull, D. M. (2006). Sequence variation in mitochondrial complex I genes: mutation or polymorphism? Journal of Medical Genetics, 43, 175-179.
52. MITOMAP. (2008). MITOMAP: A human mitochondrial genome database. Retrieved April 2, 2008, from http://www.mitomap.org
53. Mochel, F., Knight, M. A., Tong, W. H., Hernandez, D., Ayyad, K., Taivassalo, T., Andersen, P. M., Singleton, A., Rouault, T. A., Fischbeck, K. H., & Haller, R. G. (2008) Splice mutation in the iron-sulfur cluster scafold protein ISCU causes myopathy with exercise intolerance. American Journal of Human Genetics, 82, 652-660.
54. Mollet, J., Delahodde, A., Serre, V., Chretien, D., Schlemmer, D., Lombes, A., Boddaert, N., Desguerre, I., de Lonlay, P., de Baulny, H. O., Munnich, A., & Rotig, A. (2008). CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and seizures. American Journal of Human Genetics, 82, 623-630.
55. Mollet, J., Giurgea, I., Schlemmer, D., Dallner, G., Chretien, D., Delahodde, A., Bacq, D., de Lonlay, P., Munnich, A., & Rotig, A. (2007). Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders. Journal of Clinical Investigation, 117, 765-772.
56. Mootha, V. K., Lepage, P., Miller, K., Bunkenborg, J., Reich, M., Hjerrild, M., Delmonte, T., Villeneuve, A., Sladek, R., Xu, F., Mitchell, G. A., Morin, C., Mann, M., Hudson, I. J., Robinson, B., Rioux, J. D., & Lander, E. S. (2003). Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics. Proceedings of the National Academy of Sciences of the United States of America, 100, 605-610.
57. Morison, I. M., Borde, E. M., Cheesman, E. J., Cheong, P. L., Holyoake, A. J., Fichelson, S., Weeks, R. J., Lo, A., Davies, S. M., Wilbanks, S. M., Fagerlund, R. D., Ludgate, M. W., da Silva Tatley, F. M., Coker, M. S., Bockett, N. A., Hughes, G., Pippig, D. A., Smith, M. P., Capron, C., & Ledgerwood, E. C. (2008). A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia. Nature Genetics, 40, 387-389.
58. Munnich, A., & Rustin, P. (2001). Clinical spectrum and diagnosis of mitochondrial disorders. American Journal of Medical Genetics, 106, 4-17.
59. Naviaux, R. K., & Nguyen, K. V. (2004). POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. Annals of Neurology, 55, 706-712.
60. Nishino, I., Spinazzola, A., & Hirano, M. (1999). Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science, 283, 689-692.
61. Ogilvie, I., Kennaway, N. G., Shoubridge, E. A. (2005). A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy. Journal of Clinical Investigation, 115, 2784-2792.
62. Ostergaard, E., Christensen, E., Kristensen, E., Mogensen, B., Duno, M., Shoubridge, E. A., & Wibrand, F. (2007a). Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion. American Journal of Human Genetics, 81, 383-387.
63. Ostergaard, E., Hansen, F. J., Sorensen, N., Duno, M., Vissing, J., Larsen, P. L., Faeroe, O., Thorgrimsson, S., Wibrand, F., Christensen, E., & Schwartz, M. (2007b). Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations. Brain: A Journal of Neurology, 130, 853-861.
64. Papadopoulou, L. C., Sue, C. M., Davidson, M. M., Tanji, K., Nishino, I., Sadlock, J. E., Krishna, S., Walker, W., Selby, J., Glerum, D. M, Coster, R. V., Lyon, G., Scalais, E., Lebel, R., Kaplan, P., Shanske, S., De Vivo, D. C., Bonilla, E., Hirano, M., DiMauro, S., & Schon, E. A. (1999). Fatal infantile cardioen-cephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene. Nature Genetics, 23, 333-337.
65. Pequignot, M. O., Dey, R., Zeviani, M., Tiranti, V., Godinot, C., Poyau, A., Sue, C., Di Mauro, S., Abitbol, M., & Marsac, C. (2001). Mutations in the SURF1 gene associated with Leigh syndrome and cytochrome C oxidase deficiency. Human Mutation, 17, 374-381.
66. Quinzii, C., Naini, A., Salviati, L., Trevisson, E., Navas, P., DiMauro, S., & Hirano, M. (2006). A Mutation in Para-Hydroxybenzoate-Polyprenyl Transferase (COQ2) Causes Primary Coenzyme Q10 Deficiency. American Journal of Human Genetics, 78, 345-349.
67. Rotig, A., de Lonlay, P., Chretien, D., Foury, F., Koenig, M., Sjdj, D., Munnich, A., & Rustin, P. (1997). Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia. Nature Genetics, 17, 215-217.
68. Saada, A., Edvardson, S., Rapoport, M., Shaag, A., Amry, K., Miller, C., Lorberboum-Galski, H., & Elpeleg, O. (2008). C6ORF66 is an assembly factor of mitochondrial complex I. American Journal of Human Genetics, 82, 32-38.
69. Saada, A., Shaag, A., Arnon, S., Dolfin, T., Miller, C., Fuchs-Telem, D., Lombes, A., & Elpeleg, O. (2007). Antenatal mitochondrial disease caused by mitochondrial ribosomal protein (MRPS22) mutation. Journal of Medical Genetics, 44, 784-786.
70. Saada, A., Shaag, A., Mandel, H., Nevo, Y., Eriksson, S., & Elpeleg, O. (2001). Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nature Genetics, 29, 342-344.
71. Sarzi, E., Brown, M. D., Lebon, S., Chretien, D., Munnich, A., Rotig, A., Procaccio, V. (2007a). A novel recurrent mitochondrial DNA mutation in ND3 gene is associated with isolated complex I deficiency causing Leigh syndrome and dystonia. American Journal of Medical Genetics, 143, 33-41.
72. Sarzi, E., Goffart, S., Serre, V., Chretien, D., Slama, A., Munnich, A., Spelbrink, J. N., Rotig A. (2007b). Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA depletion. Annals of Neurology, 62, 579-587.
73. Schapira, A. H. (2006). Mitochondrial disease. Lancet, 368, 70-82.
74. Scheper, G. C., van, der Klok, T., van Andel, R. J., van Berkel, C. G., Sissler, M., Smet, J., Muravina, T. I., Serkov, S. V., Uziel, G., Bugiani, M., Schiffmann, R., Krageloh-Mann, I., Smeitink, J. A., Florentz, C., Van Coster, R., Pronk, J. C., van der Knaap, M. S. (2007). Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Nature Genetics, 39, 534-539.
75. Shanske, S., Coku, J., Lu, J., Ganesh, J., Krishna, S., Tanji, K., Bonilla, E., Naini, A. B., Hirano, M., & Dimauro, S. (2008). The G13513A Mutation in the ND5 gene of mitochondrial DNA as a common cause of MELAS or Leigh syndrome: Evidence From 12 cases. Archives of Neurology, 65, 368-372.
76. Shoffner, J. M. (1996). Maternal inheritance and the evaluation of oxidative phosphorylation diseases. Lancet, 348, 1283-1288.
77. Skladal, D., Halliday, J., & Thorburn, D. R. (2003). Minimum birth prevalence of mitochondrial respiratory chain disorders in children. Brain: A Journal of Neurology, 126, 1905-1912.
78. Smeitink, J. A., Elpeleg, O., Antonicka, H., Diepstra, H., Saada, A., Smits, P., Sasarman, F., Vriend, G., Jacob-Hirsch, J., Shaag, A., Rechavi, G., Welling, B., Horst, J., Rodenburg, R. J., van den Heuvel, B., & Shoubridge, E. A. (2006). Distinct Clinical Phenotypes Associated with a mutation in the mitochondrial translation elongation factor EFTs. American Journal of Human Genetics, 79, 869-877.
79. Spelbrink, J. N., Li, F. Y., Tiranti, V., Nikali, K., Yuan, Q. P., Tariq, M., Wanrooij, S., Garrido, N., Comi, G., Morandi, L., Santoro, L., Toscano, A., Fabrizi, G. M., Somer, H., Croxen, R., Beeson, D., Poulton, J., Suomalainen, A., Jacobs, H. T., Zeviani, M., & Larsson, C. (2001). Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria. Nature Genetics, 28, 223-231.
80. Spinazzola, A., Viscomi, C., Fernandez-Vizarra, E., Carrara, F., D'Adamo, P., Calvo, S., Marsano, R. M., Donnini, C., Weiher, H., Strisciuglio, P., Parini, R., Sarzi, E., Chan, A., DiMauro, S., Rotig, A., Gasparini, P., Ferrero, I., Mootha, V. K., Tiranti, V., & Zeviani, M. (2006). MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion. Nature Genetics, 38, 570-575.
81. Stenson, P. D., Ball, E. V., Mort, M., Phillips, A. D., Shiel, J. A., Thomas, N. S., Abeysinghe, S., Krawczak, M., & Cooper, D. N. (2003) Human Gene Mutation Database (HGMD): 2003 update. Human Mutation, 21, 577-581.
82. Taylor, R. W, & Turnbull, D. M. (2005). Mitochondrial DNA mutations in human disease. Nature Reviews - Genetics, 6, 389-402.
83. Thorburn, D. R. (2004). Mitochondrial disorders: Prevalence, myths and advances. Journal of Inherited Metabolic Disorders, 27, 349-362.
84. Thorburn, D. R., Chow, C. W., & Kirby, D. M. (2004a). Respiratory Chain Enzyme Analysis in Muscle and Liver. Mitochondrion, 4, 363-375.
85. Thorburn, D. R., & Rahman, S. Mitochondrial DNA-associated Leigh syndrome and NARP: GeneReviews at GeneTests: Medical genetics information resource [database online]. Copyright, University of Washington, Seattle, 1997-2003, 2003.
86. Thorburn, D. R., Sugiana, C., Salemi, R., Kirby, D. M., Worgan, L., Ohtake, A., & Ryan, M. T. (2004b). Biochemical and molecular diagnosis of mitochondrial respiratory chain disorders. Biochim Biophys Acta Bioenergetics, 1659, 121-128.
87. Tiranti, V., D'Adamo, P., Briem, E., Ferrari, G., Mineri, R., Lamantea, E., Mandel, H., Balestri, P., Garcia-Silva, M. T., Vollmer, B., Rinaldo, P., Hahn, S. H., Leonard, J., Rahman, S., Dionisi-Vici, C., Garavaglia, B., Gasparini, P., & Zeviani, M. (2004). Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein. American Journal of Human Genetics, 74, 239-252.
88. Tiranti, V., Hoertnagel, K., Carrozzo, R., Galimberti, C., Munaro, M., Granatiero, M., Zelante, L., Gasparini, P., Marzella, R., Rocchi, M., Bayona-Bafaluy, M. P., Enriquez, J. A., Uziel, G., Bertini, E., Dionisi-Vici, C., Franco, B., Meitinger, T., & Zeviani, M. (1998). Mutations of SURF-i in Leigh disease associated with cytochrome c oxidase deficiency. American Journal of Human Genetics, 63, 1609-1621.
89. Triepels, R. H, van den Heuvel, L. P., Loeffen, J. L., Buskens, C. A., Smeets, R. J., Rubio Gozalbo, M. E., Budde, S. M., Mariman, E. C., Wijburg, F. A., Barth, P.G., Trijbels, J. M., & Smeitink, J. A. (1999). Leigh syndrome associated with a mutation in the NDUFS7 (PSST) nuclear encoded subunit of complex I. Annals of Neurology, 45, 787-790.
90. Valente, L., Tiranti, V., Marsano, R.M., Malfatti, E., Fernandez-Vizarra, E., Donnini, C., Mereghetti, P., De Gioia, L., Burlina, A., Castellan, C., Comi, G.P., Savasta, S., Ferrero, I. & Zeviani, M. (2007). Infantile encephalopathy and defective mitochondrial DNA translation in patients with mutations of mitochondrial elongation factors EFG1 and EFTu. American Journal of Human Genetics, 80, 44-58.
91. Valnot, I., Osmond, S., Gigarel, N., Mehaye, B., Amiel, J., Cormier-Daire, V., Munnich, A., Bonnefont, J. P., Rustin, P., & Rotig, A. (2000a). Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy. American Journal of Human Genetics, 67, 1104-1109.
92. Valnot, I., von Kleist-Retzow, J. C, Barrientos, A., Gorbatyuk, M., Taanman, J. W., Mehaye, B., Rustin, P., Tzagoloff, A., Munnich, A., & Rotig, A. (2000b). A mutation in the human heme a:farnesyltransferase gene (COX10) causes cytochrome c oxidase deficiency. Human Molecular Genetics, 9, 1245-1249.
93. van den Heuvel, L., Ruitenbeek, W, Smeets, R., Gelman-Kohan, Z., Elpeleg, O., Loeffen, J., Trijbels, F., Mariman, E., de Bruijn, D., & Smeitink, J. (1998). Demonstration of a new pathogenic mutation in human complex I deficiency: A 5-bp duplication in the 18-kD (AQDQ) subunit. American Journal of Human Genetics, 62, 262-268.
94. Van Goethem, G., Dermaut, B., Lofgren, A., Martin, J. J., & Van Broeckhoven, C. (2001). Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nature Genetics, 28, 211-212.
95. Visapaa, I., Fellman, V., Vesa, J. Dasvarma, A., Hutton, J. L., Kumar, V., Payne, G. S., Makarow, M., Van Coster, R., Taylor, R. W, Turnbull, D. M., Suomalainen, A., & Peltonen, L. (2002). GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused by a point mutation in BCS1L. American Journal of Human Genetics, 71, 863-876.
96. Vreken, P., Valianpour, F., Nijtmans, L. G., Grivell, L. A., Plecko, B., Wanders, R. J, Barth, P. G. (2000). Defective remodeling of cardiolipin and phosphatidylglycerol in Barth syndrome. Biochemical and Biophysical Research Communications, 279, 378-382.
97. Wallace, D. C, Singh, G., Lott, M. T., Hodge, J. A., Schurr, T. G., Lezza, A. M. S, Elsas, L. J., & Nikoskelainen, E. K. (1988). Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science, 242, 1427-1430.
98. Wimplinger, I., Morleo, M., Rosenberger, G., Iaconis, D., Orth, U., Meinecke, P., Lerer, I., Ballabio, A., Gal, A., Franco, B., & Kutsche, K. (2006). Mutations of the mitochondrial holocytochrome c-type synthase in x-linked dominant microphthalmia with linear skin defects syndrome. American Journal of Human Genetics, 79, 878-889.
99. Xu, F., Morin, C., Mitchell, G., Ackerley, C., & Robinson, B. H. (2004). The role of the LRPPRC (leucine-rich pentatricopeptide repeat cassette) gene in cytochrome oxidase assembly: Mutation causes lowered levels of COX (cytochrome c oxidase) I and COX III mRNA. Biochemical Journal, 382, 331-336.
100. Zeviani, M., & Di Donato, S. (2004). Mitochondrial disorders. Brain: A Journal of Neurology, 127, 2153-2172.
101. Zhang, Y., Yang, Y L., Sun, F., Cai, X., Qian, N., Yuan, Y., Wang, Z. X., Qi, Y., Xiao, J. X, Wang, X. Y., Zhang, Y. H., Jiang, Y. W., Qin, J., Wu, X. R. (2007). Clinical and molecular survey in 124 Chinese patients with Leigh or Leigh-like syndrome. Journal of Inherited Metabolic Disease, 30, 265.
102. Zhu, Z., Yao, J., Johns, T., Fu, K., De Bie, I., Macmillan, C., Cuthbert, A. P., Newbold, R. F., Wang, J., Chevrette, M., Brown, G. K., Brown, R. M., & Shoubridge, E. A. (1998). SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome. Nature Genetics, 20, 337-343.
103. Zuchner, S., Mersiyanova, I. V., Muglia, M., Bissar-Tadmouri, N., Rochelle, J., Dadali, E. L., Zappia, M., Nelis, E., Patitucci, A., Senderek, J., Parman, Y., Evgrafov, O., Jonghe, P. D, Takahashi, Y., Tsuji, S., Pericak-Vance, M. A., Quattrone, A., Battaloglu, E., Polyakov, A. V., Timmerman, V., Schroder, J. M., & Vance, J. M. (2004). Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nature Genetics, 36, 449-451.