Non-Structural Nuclear Genes in Mitochondrial Disease

Last update: March 2012

Complex Assembly

Complex Name OMIM Function Chromosome Inheritance Clinical Phenotype References
I NDUFAF1(CIA30) 606934 Assembly 15q13.3 AR Cardioencephalomyopathy (26)
I NDUFAF2(B17.2L) 609653 Assembly 5q12.1 AR Early onset progressive encephalopathy (45)
I NDUFAF3 612911 Assembly 3p21.31 AR Neonatal encephalopathy (13)
I NDUFAF4(HRPAP20) 611776 Assembly 6q16.1 AR Infantile encephalopathy (23)
I C20orf7 612360 Assembly 20p12.1 AR LS (6,24)
I NUBPL 613621 Assembly 14q12 AR Encephalomyopathy (5)
I FOXRED1 613622 Unknown 11q24.2 AR LS (5)
I ACAD9 611103 Assembly and activity 3q26 AR Hypertrophic cardiopathy encephalopathy (7)
II SDHAF1 612848 Assembly 19q12-q13.2 AR Leukoencephalopathy (10)
II SDHAF2 613019 Assembly 11q12.2 AD Autosomal dominant paraganglioma type 2 (12)
III BCS1L 603647 Assembly 2q33 AR Encephalopathy, hepatic failure and tubulopathy, LS, GRACILE syndrome, Bjornstad Syndrome (28,59,60)
IV SURF1 185620 Assembly 9q34 AR LS (75,76)
IV SCO1 603644 Copper transport 17p13-p12 AR Neonatal hepatic failure and encephalopathy (70)
IV SCO2 604272 Copper transport 22q13 AR Neonatal Cardioencephalomyopathy (73)
IV COX10 602125 Heme A farnesyltransferase 17p12-p11.2 AR Neonatal tubulopathy and encephalopathy, LS, cardiomyopathy (55,70)
IV COX15 603646 Heme A synthesis 10q24 AR Early-onset hypertrophic cardiomyopathy, LS (52,56)
IV LRPPRC 220111 Assembly 2p21-p16 AR French-Canadian LS (57)
IV FASTKD2 612322 Role in apoptosis 2q33.3 AR Encephalomyopathy (19)
IV TACO1 612958 Translational activator of COX1 17q22-q24.2 AR LS (16)
V ATPAF2 608918 Assembly 17p11.2 AR Early-onset encephalopathy, Lactic acidosis (49)
V TMEM70 604273 Assembly 8q21.11 AR Neonatal encephalopathy, cardiomyopathy (18)

MtDNA Stability

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
POLG (PEOA1) 174763 Polymerase gamma mtDNA replication 15q25 AD-AR Alpers syndrome, AD-PEO and AR-PEO, male infertility, SANDO* syndrome, SCAE* (51,63,66)
POLG2 (PEOA4) 610131 catalytic subunit of DNA polymerase gamma 17q23-q24 AD AD-PEO (36)
ANT1 (PEOA2) 609283 ADenine nucleotide translocator isoform 1 4q35 AD AD-PEO, multiple mtDNA deletions (69)
MPV17 137960 regulation of mtDNA copy number 2p23-p21 AR Hepatocerebral MDDS (40)
C10ORF2 (PEOA3) 609286 Twinkle helicase 10q24 AD AD-PEO, SANDO syndrome (43,65)
TYMP (ECGF1) 603041 Thymidine phosphorylase 22q13.32-qter AR MNGIE, mtDNA depletion (72)
DGUOK 601465 Deoxyguanosine kinase Mitochondrial dNTP pool maintenance 2p13 AR Hepatocerebral mtDNA depletion syndrome (61)
RRM2B (PEOA5) 604712 ribonucleotide reductase M2 B dNTP pool 8q23.1 AR Encephalomyopathic Renal tubulopathy MNGIE, AD-PEO (14,15,25)
SUCLA2 603921 succinate-CoA ligase, ADP-forming, beta subunit 13q12.2-q13 AR Encephalomyopathy with methylmalonic aciduria (42)
SUCLG1 611224 succinate-CoA ligase, alpha subunit 2p11.2 AR Encephalomyopathy with methylmalonic aciduria (30)
TK2 188250 Thymidine kinase Mitochondrial dNTP pool maintenance 16q22 AR Myopathic mtDNA depletion (64)

Mitochondrial Import

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
DDP 304700 Protein import Xq22 X-linked Deafness-dystonia or Mohr-Tranebjaerg syndrome (81)
DNAJC19 608977 Protein import 3q26.3 AR Cardiomyopathy, ataxia (35)

Mitochondrial Protein Synthesis

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
EFG1 609060 Elongation factor G1; mitochondrial translation defect 3q25 AR Severe hepatoencephalopathy and lactic acidosis (48)
YARS2 610957 tyrosyl-tRNA synthetase 12p11.21 AR myopathy, lactic acidosis, and sideroblastic anemia-2 (8)
SARS2 612804 seryl-tRNA synthetase 19q13.2 AR Hyperuricemia, pulmonary hypertension, renal failure (3)
DARS2 611105 aspartyl-tRNA synthetase 1q25.1 AR Leukoencephalopathy and lactic acidosis (32)
RARS2 611523 ARginyl-tRNA synthetase 6q16.1 AR Pontocerebellar hypoplasia (27)
MRPS16 609204 Mitochondrial translation 10q22.1 AR neonatal lactic acidosis corpus callosum agenesis (50)
MRPS22 605810 Mitochondrial translation 3q23 AR cardiomyopathy, tubulopathy (31)
TSFM 604723 Mitochondrial translation elongation 12q13-q14 AR Encephalomyopathy, hypertrophic cardiomyopathy (39)
TUFM 602389 Mitochondrial translation elongation 16p11.2 AR leukodystrophy with micropolygyria (33)

Iron Homeostasis

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
FRDA 606829 Frataxin Trinuc. repeat 9q13 AR Friedreich ataxia, neuropathy, cardiomyopathy, diabetes (78,80)
ABCB7 301310 Iron transport Xq13.1-q13.3 X-linked X-linked sideroblastic anemia with ataxia (71)
GLRX5 205950 Iron-sulfur cluster biosynthesis 3p22.1 AR Sideroblastic anemia (11)
ISCU 255125 Iron-sulfur cluster biosynthesis 12q23.3 AR Myopathy, lactic acidosis, exercise intolerance (21)
BOLA3 613183 Iron-sulfur cluster biosynthesis 2p13.1 AR encephalomyopathy, cardiomyopathy (4)
NFU1 608100 Iron-sulfur cluster biosynthesis 2p13.3 AR lactic acidosismultiple respiratory chain deficiency (4)

Coenzyme Q10 biogenesis

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
COQ2 609825 CoQ10 deficiency 4q21-q22 AR Encephalomyopathy, nephropathy (38)
COQ4 612898 CoQ10 deficiency 9q34.13 AR Encephalomyopathy, mental retardation (2)
COQ9 612837 CoQ10 deficiency 16q13 AR Neonatal lactic acidosis Seizures, cardiomyopathy (9)
APTX 606350 CoQ10 deficiency 9p13.3 AR Cerebellar ataxia oculomotor apraxia (46)
PDSS1 607429 CoQ10 deficiency 10p12.1 AR Deafness, valvulopathy, mental retardation (29)
PDSS2 610564 CoQ10 deficiency 6q21 AR LS, nephrotic syndrome (37)
CABC1 606980 CoQ10 deficiency 1q42.2 AR Cerebellar ataxia, lactic acidosis (22)

Chaperone Function

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
SPG7 607259 Paraplegin ATPase protease 16q24.3 AR Spastic paraplegia (74)
HSPD1 118190 Mitochondrial chaperone 2q33.1 AR Spastic paraplegia, leukodystrophy (20)

Mitochondrial Integrity

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
OPA1 165500 Dynamin-related protein 3q28-q29 AD AD-Optic Atrophy
Multiple deletions
MFN2 609260 Mitofusin Mitochondrial fusion 1p36-p35 AD Charcot-Marie-Tooth Disease-2A2 (CMT2A2)
Multiple deletions
DLP1 603850 Mitochondrial and peroxisomal fission 12p11.21 AD Microcephaly, abnormal brain development, optic atrophy, lactic acidosis (34)
G4.5 (Tafazzin) 302060 Cardiolipin defect Xq28 X-linked Barth syndrome, X-linked dilated cardiomyopathy (77,79)
RMRP 250250 RNAse Mitochondrial RNA Processing 9p13-p12 AR Metaphyseal chondrodysplasia or Cartilage-hair hypoplasia (58,62)

Mitochondrial Metabolism

Name OMIM Function Chromosome Inheritance Clinical Phenotype References
PDHA1 308930 Pyruvate dehydrogenase E1-α subunit Xp22.2-p22.1 X-linked LS (82)
ETHE1 602473 Ethylmalonic acid metabolism 19q13 AR Encephalopathy, ethylmalonic aciduria (41,53)
PUS1 600462 pseudouridine synthase 12q24.33 AR myopathy, lactic acidosis, and sideroblastic anemia (47)

Abbreviations LS: Leigh Syndrome; SANDO: Sensory Ataxic Neuropathy, Dysarthria, and Ophthalmoparesis; SCAE: Spinocerebellar Ataxia with Epilepsy; GRACILE syndrome: Growth Retardation, Amino aciduria, Cholestasis, Iron overload, Lactic acidosis, and Early death; MNGIE: Mitochondrial NeuroGastroIntestinal Encephalopathy; MDDS: Mitochondrial DNA Depletion Syndrome


1. Rouzier, C., Bannwarth, S., Chaussenot, A., Chevrollier, A., Verschueren, A., Bonello-Palot, N., Fragaki, K., Cano, A., Pouget, J., Pellissier, J. F., Procaccio, V., Chabrol, B. and Paquis-Flucklinger, V. (2012). "The MFN2 gene is responsible for mitochondrial DNA instability and optic atrophy 'plus' phenotype". Brain 135(Pt 1):23-34.

2. Salviati, L., Trevisson, E., Rodriguez Hernandez, M. A., Casarin, A., Pertegato, V., Doimo, M., Cassina, M., Agosto, C., Desbats, M. A., Sartori, G., Sacconi, S., Memo, L., Zuffardi, O., Artuch, R., Quinzii, C., Dimauro, S., Hirano, M., Santos-Ocana, C. and Navas, P. (2012). "Haploinsufficiency of COQ4 causes coenzyme Q10 deficiency". Journal of Medical Genetics 49(3):187-191.

3. Belostotsky, R., Ben-Shalom, E., Rinat, C., Becker-Cohen, R., Feinstein, S., Zeligson, S., Segel, R., Elpeleg, O., Nassar, S. and Frishberg, Y. (2011). "Mutations in the mitochondrial seryl-tRNA synthetase cause hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis, HUPRA syndrome". American Journal of Human Genetics 88(2):193-200.

4. Cameron, J. M., Janer, A., Levandovskiy, V., Mackay, N., Rouault, T. A., Tong, W. H., Ogilvie, I., Shoubridge, E. A. and Robinson, B. H. (2011). "Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes". American Journal of Human Genetics 89(4):486-495.

5. Calvo, S. E., Tucker, E. J., Compton, A. G., Kirby, D. M., Crawford, G., Burtt, N. P., Rivas, M., Guiducci, C., Bruno, D. L., Goldberger, O. A., Redman, M. C., Wiltshire, E., Wilson, C. J., Altshuler, D., Gabriel, S. B., Daly, M. J., Thorburn, D. R. and Mootha, V. K. (2010). "High- throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency". Nature Genetics 42(10):851-588.

6. Gerards, M., Sluiter, W., van den Bosch, B. J., de Wit, L. E., Calis, C. M., Frentzen, M., Akbari, H., Schoonderwoerd, K., Scholte, H. R., Jongbloed, R. J., Hendrickx, A. T., de Coo, I. F. and Smeets, H. J. (2010). "Defective complex I assembly due to C20orf7 mutations as a new cause of Leigh syndrome". Journal of Medical Genetics 47(8):507-512.

7. Haack, T. B., Danhauser, K., Haberberger, B., Hoser, J., Strecker, V., Boehm, D., Uziel, G., Lamantea, E., Invernizzi, F., Poulton, J., Rolinski, B., Iuso, A., Biskup, S., Schmidt, T., Mewes, H. W., Wittig, I., Meitinger, T., Zeviani, M. and Prokisch, H. (2010). "Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency". Nature Genetics 42(12):1131-1134.

8. Riley, L. G., Cooper, S., Hickey, P., Rudinger-Thirion, J., McKenzie, M., Compton, A., Lim, S. C., Thorburn, D., Ryan, M. T., Giege, R., Bahlo, M. and Christodoulou, J. (2010). "Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia--MLASA syndrome". American Journal of Human Genetics 87(1):52- 59.

9. Duncan, A. J., Bitner-Glindzicz, M., Meunier, B., Costello, H., Hargreaves, I. P., Lopez, L. C., Hirano, M., Quinzii, C. M., Sadowski, M. I., Hardy, J., Singleton, A., Clayton, P. T. and Rahman, S. (2009). "A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease". American Journal of Human Genetics 84(5):558-566.

10. Ghezzi, D., Goffrini, P., Uziel, G., Horvath, R., Klopstock, T., Lochmuller, H., D'Adamo, P., Gasparini, P., Strom, T. M., Prokisch, H., Invernizzi, F., Ferrero, I. and Zeviani, M. (2009). "SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy". Nature Genetics 41(6):654-656.

11. Guernsey, D. L., Jiang, H., Campagna, D. R., Evans, S. C., Ferguson, M., Kellogg, M. D., Lachance, M., Matsuoka, M., Nightingale, M., Rideout, A., Saint-Amant, L., Schmidt, P. J., Orr, A., Bottomley, S. S., Fleming, M. D., Ludman, M., Dyack, S., Fernandez, C. V. and Samuels, M. E. (2009). "Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia". Nature Genetics 41(6):651-653.

12. Hao, H. X., Khalimonchuk, O., Schraders, M., Dephoure, N., Bayley, J. P., Kunst, H., Devilee, P., Cremers, C. W., Schiffman, J. D., Bentz, B. G., Gygi, S. P., Winge, D. R., Kremer, H. and Rutter, J. (2009). "SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma". Science 325(5944):1139-1142.

13. Saada, A., Vogel, R. O., Hoefs, S. J., van den Brand, M. A., Wessels, H. J., Willems, P. H., Venselaar, H., Shaag, A., Barghuti, F., Reish, O., Shohat, M., Huynen, M. A., Smeitink, J. A., van den Heuvel, L. P. and Nijtmans, L. G. (2009). "Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting complex I assembly protein, cause fatal neonatal mitochondrial disease". American Journal of Human Genetics 84(6):718-727.

14. Shaibani, A., Shchelochkov, O. A., Zhang, S., Katsonis, P., Lichtarge, O., Wong, L. J. and Shinawi, M. (2009). "Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B". Archives of Neurology 66(8):1028-1032.

15. Tyynismaa, H., Ylikallio, E., Patel, M., Molnar, M. J., Haller, R. G. and Suomalainen, A. (2009). "A heterozygous truncating mutation in RRM2B causes autosomal-dominant progressive external ophthalmoplegia with multiple mtDNA deletions". American Journal of Human Genetics 85(2):290-295.

16. Weraarpachai, W., Antonicka, H., Sasarman, F., Seeger, J., Schrank, B., Kolesar, J. E., Lochmuller, H., Chevrette, M., Kaufman, B. A., Horvath, R. and Shoubridge, E. A. (2009). "Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome". Nature Genetics 41(7):833-837.

17. Amati-Bonneau, P., Valentino, M. L., Reynier, P., Gallardo, M. E., Bornstein, B., et al. (2008). "OPA1 mutations induce mitochondrial DNA instability and optic atrophy 'plus' phenotypes". Brain 131(Pt 2):338-351.

18. Cizkova, A., Stranecky, V., Mayr, J. A., Tesarova, M., Havlickova, V., et al. (2008). "TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy". Nature Genetics 40(11):1288-1290.

19. Ghezzi, D., Saada, A., D'Adamo, P., Fernandez-Vizarra, E., Gasparini, P., Tiranti, V., Elpeleg, O. and Zeviani, M. (2008). "FASTKD2 nonsense mutation in an infantile mitochondrial encephalomyopathy associated with cytochrome c oxidase deficiency". American Journal of Human Genetics 83(3):415-423.

20. Magen, D., Georgopoulos, C., Bross, P., Ang, D., Segev, Y., Goldsher, D., Nemirovski, A., Shahar, E., Ravid, S., Luder, A., Heno, B., Gershoni-Baruch, R., Skorecki, K. and Mandel, H. (2008). "Mitochondrial hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy". American Journal of Human Genetics 83(1):30- 42.

21. 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. and Haller, R. G. (2008). "Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance". American Journal of Human Genetics 82(3):652-660.

22. 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. and Rotig, A. (2008). "CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and seizures". American Journal of Human Genetics 82(3):623-630.

23. Saada, A., Edvardson, S., Rapoport, M., Shaag, A., Amry, K., Miller, C., Lorberboum-Galski, H. and Elpeleg, O. (2008). "C6ORF66 is an assembly factor of mitochondrial complex I". American Journal of Human Genetics 82(1):32-38.

24. Sugiana, C., Pagliarini, D. J., McKenzie, M., Kirby, D. M., Salemi, R., Abu-Amero, K. K., Dahl, H. H., Hutchison, W. M., Vascotto, K. A., Smith, S. M., Newbold, R. F., Christodoulou, J., Calvo, S., Mootha, V. K., Ryan, M. T. and Thorburn, D. R. (2008). "Mutation of C20orf7 disrupts complex I assembly and causes lethal neonatal mitochondrial disease". American Journal of Human Genetics 83(4):468-478.

25. 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. and Rotig, A. (2007). "Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion". Nature Genetics 39(6):776-780.

26. Dunning, C. J., McKenzie, M., Sugiana, C., Lazarou, M., Silke, J., Connelly, A., Fletcher, J. M., Kirby, D. M., Thorburn, D. R. and 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(13):3227-3237.

27. Edvardson, S., Shaag, A., Kolesnikova, O., Gomori, J. M., Tarassov, I., Einbinder, T., Saada, A. and Elpeleg, O. (2007). "Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia". American Journal of Human Genetics 81(4):857-862.

28. 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. and Seidman, C. E. (2007). "Missense mutations in the BCS1L gene as a cause of the Bjornstad syndrome". The New England Journal of Medicine 356(8):809-819.

29. Mollet, J., Giurgea, I., Schlemmer, D., Dallner, G., Chretien, D., Delahodde, A., Bacq, D., de Lonlay, P., Munnich, A. and Rotig, A. (2007). "Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders". The Journal of Clinical Investigation 117(3):765-772.

30. Ostergaard, E., Christensen, E., Kristensen, E., Mogensen, B., Duno, M., Shoubridge, E. A. and Wibrand, F. (2007). "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(2):383-387.

31. Saada, A., Shaag, A., Arnon, S., Dolfin, T., Miller, C., Fuchs-Telem, D., Lombes, A. and Elpeleg, O. (2007). "Antenatal mitochondrial disease caused by mitochondrial ribosomal protein (MRPS22) mutation". Journal of Medical Genetics 44(12):784-786.

32. 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. and 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(4):534-539.

33. 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. and 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(1):44-58.

34. Waterham, H. R., Koster, J., van Roermund, C. W., Mooyer, P. A., Wanders, R. J. and Leonard, J. V. (2007). "A lethal defect of mitochondrial and peroxisomal fission". The New England Journal of Medicine 356(17):1736-1741.

35. Davey, K. M., Parboosingh, J. S., McLeod, D. R., Chan, A., Casey, R., Ferreira, P., Snyder, F. F., Bridge, P. J. and 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(5):385-393.

36. Longley, M. J., Clark, S., Yu Wai Man, C., Hudson, G., Durham, S. E., Taylor, R. W., Nightingale, S., Turnbull, D. M., Copeland, W. C. and Chinnery, P. F. (2006). "Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia". American Journal of Human Genetics 78(6):1026-1034.

37. Lopez, L. C., Schuelke, M., Quinzii, C. M., Kanki, T., Rodenburg, R. J., Naini, A., Dimauro, S. and 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(6):1125-1129.

38. Quinzii, C., Naini, A., Salviati, L., Trevisson, E., Navas, P., Dimauro, S. and Hirano, M. (2006). "A mutation in para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency". American Journal of Human Genetics 78(2):345-349.

39. 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. and Shoubridge, E. A. (2006). "Distinct clinical phenotypes associated with a mutation in the mitochondrial translation elongation factor EFTs". American Journal of Human Genetics 79(5):869-877.

40. Spinazzola, A., Viscomi, C., Fernandez-Vizarra, E., Carrara, F., D'Adamo, P., et al. (2006). "MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion". Nature Genetics 38(5):570-575.

41. Tiranti, V., Briem, E., Lamantea, E., Mineri, R., Papaleo, E., Degioia, L., Forlani, F., Rinaldo, P., Dickson, P., Abu-Libdeh, B., Cindro-Heberle, L., Owaidha, M., Jack, R. M., Christensen, E., Burlina, A. and Zeviani, M. (2006). "ETHE1 mutations are specific to ethylmalonic encephalopathy". Journal of Medical Genetics 43(4):340-346.

42. Elpeleg, O., Miller, C., Hershkovitz, E., Bitner-Glindzicz, M., Bondi-Rubinstein, G., Rahman, S., Pagnamenta, A., Eshhar, S. and Saada, A. (2005). "Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion". American Journal of Human Genetics 76(6):1081-1086.

43. Hudson, G., Deschauer, M., Busse, K., Zierz, S. and Chinnery, P. F. (2005). "Sensory ataxic neuropathy due to a novel C10Orf2 mutation with probable germline mosaicism". Neurology 64(2):371-373.

44. Kijima, K., Numakura, C., Izumino, H., Umetsu, K., Nezu, A., Shiiki, T., Ogawa, M., Ishizaki, Y., Kitamura, T., Shozawa, Y. and Hayasaka, K. (2005). "Mitochondrial GTPase mitofusin 2 mutation in Charcot-Marie-Tooth neuropathy type 2A". Human Genetics 116(1-2):23-27.

45. Ogilvie, I., Kennaway, N. G. and Shoubridge, E. A. (2005). "A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy". The Journal of Clinical Investigation 115(10):2784-2792.

46. Quinzii, C. M., Kattah, A. G., Naini, A., Akman, H. O., Mootha, V. K., DiMauro, S. and Hirano, M. (2005). "Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation". Neurology 64(3):539-541.

47. Bykhovskaya, Y., Casas, K., Mengesha, E., Inbal, A. and Fischel-Ghodsian, N. (2004). "Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA)". American Journal of Human Genetics 74(6):1303-1308.

48. 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. and Smeitink, J. A. (2004). "Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency". The New England Journal of Medicine 351(20):2080-2086.

49. De Meirleir, L., Seneca, S., Lissens, W., De Clercq, I., Eyskens, F., Gerlo, E., Smet, J. and Van Coster, R. (2004). "Respiratory chain complex V deficiency due to a mutation in the assembly gene ATP12". Journal of Medical Genetics 41(2):120-124.

50. Miller, C., Saada, A., Shaul, N., Shabtai, N., Ben-Shalom, E., Shaag, A., Hershkovitz, E. and Elpeleg, O. (2004). "Defective mitochondrial translation caused by a ribosomal protein (MRPS16) mutation". Annals of Neurology 56(5):734-738.

51. Naviaux, R. K. and Nguyen, K. V. (2004). "POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion". Annals of Neurology 55(5):706-712.

52. Oquendo, C. E., Antonicka, H., Shoubridge, E. A., Reardon, W. and Brown, G. K. (2004). "Functional and genetic studies demonstrate that mutation in the COX15 gene can cause Leigh syndrome". Journal of Medical Genetics 41(7):540-544.

53. 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. and Zeviani, M. (2004). "Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein". American Journal of Human Genetics 74(2):239-252.

54. Zuchner, S., Mersiyanova, I. V., Muglia, M., Bissar-Tadmouri, N., Rochelle, J., et al. (2004). "Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A". Nature Genetics 36(5):449-451.

55. Antonicka, H., Leary, S. C., Guercin, G. H., Agar, J. N., Horvath, R., Kennaway, N. G., Harding, C. O., Jaksch, M. and Shoubridge, E. A. (2003). "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". Human Molecular Genetics 12(20):2693-2702.

56. Antonicka, H., Mattman, A., Carlson, C. G., Glerum, D. M., Hoffbuhr, K. C., Leary, S. C., Kennaway, N. G. and 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(1):101- 114.

57. 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, T. J., Robinson, B., Rioux, J. D. and 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(2):605- 610.

58. Ridanpaa, M., Sistonen, P., Rockas, S., Rimoin, D. L., Makitie, O. and Kaitila, I. (2002). "Worldwide mutation spectrum in cartilage-hair hypoplasia: ancient founder origin of the major70A-->G mutation of the untranslated RMRP". European Journal of Human Genetics 10(7):439- 447.

59. 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. and 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(4):863-876.

60. 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. and 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(1):57-60.

61. Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S. and Cohen, N. (2001). "The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA". Nature Genetics 29(3):337-341.

62. Ridanpaa, M., van Eenennaam, H., Pelin, K., Chadwick, R., Johnson, C., Yuan, B., vanVenrooij, W., Pruijn, G., Salmela, R., Rockas, S., Makitie, O., Kaitila, I. and de la Chapelle, A. (2001). "Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, Cartilage-Hair Hypoplasia". Cell 104(2):195-203.

63. Rovio, A. T., Marchington, D. R., Donat, S., Schuppe, H. C., Abel, J., et al. (2001). "Mutations at the mitochondrial DNA polymerase (POLG) locus associated with male infertility". Nature Genetics 29(3):261-262.

64. Saada, A., Shaag, A., Mandel, H., Nevo, Y., Eriksson, S. and Elpeleg, O. (2001). "Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy". Nature Genetics 29(3):342-344.

65. Spelbrink, J. N., Li, F. Y., Tiranti, V., Nikali, K., Yuan, Q. P., et al. (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(3):223-231.

66. Van Goethem, G., Dermaut, B., Lofgren, A., Martin, J. J. and Van Broeckhoven, C. (2001). "Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions". Nature Genetics 28(3):211-212.

67. Alexander, C., Votruba, M., Pesch, U. E. A., Thiselton, D. L., Mayer, S., Moore, A., Rodriquez, M., Kellner, U., Leo-Kottler, B., Auburger, G., Bhattcharya, S. S. and Wissinger, B. (2000). "OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28". Nature Genetics 26(2):211-215.

68. 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. and Hamel, C. P. (2000). "Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy". Nature Genetics 26(2):207-210.

69. Kaukonen, J., Juselius, J. K., Tiranti, V., Kyttala, A., Zeviani, M., Comi, G. P., Keranen, S., Peltonen, L. and Suomalainen, A. (2000). "Role of adenine nucleotide translocator 1 in mtDNA maintenance". Science 289(5480):782- 785.

70. Valnot, I., Osmond, S., Gigarel, N., Mehaye, B., Amiel, J., Cormier-Daire, V., Munnich, A., Bonnefont, J. P., Rustin, P. and Rotig, A. (2000). "Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy". American Journal of Human Genetics 67(5):1104-1109.

71. Allikmets, R., Raskind, W. H., Hutchinson, A., Schueck, N. D., Dean, M. and 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(5):743-749.

72. Nishino, I., Spinazzola, A. and Hirano, M. (1999). "Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder". Science 283(5402):689-692.

73. Papadopoulou, L. C., Sue, C. M., Davidson, M. M., Tanji, K., Nishino, I., et al. (1999). "Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene". Nature Genetics 23(3):333-337.

74. 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. and Ballabio, A. (1998). "Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease". Cell 93(6):973-983.

75. 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. and Zeviani, M. (1998). "Mutations of SURF-1 in Leigh Disease associated with cytochrome c oxidase deficiency". American Journal of Human Genetics 63(6):1609-1621.

76. 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. and Shoubridge, E. A. (1998). "SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome". Nature Genetics 20(4):337-343.

77. D'Adamo, P., Fassone, L., Gedeon, A., Janssen, E. A., Bione, S., Bolhuis, P. A., Barth, P. G., Wilson, M., Haan, E., Orstavik, K. H., Patton, M. A., Green, A. J., Zammarchi, E., Donati, M. A. and Toniolo, D. (1997). "The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies". American Journal of Human Genetics 61(4):862-867.

78. Rotig, A., de Lonlay, P., Chretien, D., Foury, F., Koenig, M., Sidi, D., Munnich, A. and Rustin, P. (1997). "Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia". Nature Genetics 17(2):215-217.

79. Bione, S., D'Adamo, P., Maestrini, E., Gedeon, A. K., Bolhuis, P. A. and Toniolo, D. (1996). "A novel X- linked gene, G4.5. is responsible for Barth syndrome". Nature Genetics 12(4):385-389.

80. Campuzano, V., Montermini, L., Molto, M. D., Pianese, L., Cossee, M., et al. (1996). Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion". Science 271(5254):1423-1427.

81. Jin, H., May, M., Tranebjaerg, L., Kendall, E., Fontan, G., Jackson, J., Subramony, S. H., Arena, F., Lubs, H., Smith, S., Stevenson, R., Schwartz, C. and Vetrie, D. (1996). "A novel X- linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness". Nature Genetics 14(2):177-180.

82. Matthews, P. M., Marchington, D. R., Squier, M., Land, J., Brown, R. M. and Brown, G. K. (1993). "Molecular genetic characterization of an X-linked form of Leigh's syndrome". Annals of Neurology 33(6):652-655.

The original version of this table was posted in 2006, reproduced with permission from PRINCIPLES AND PRACTICE OF MEDICAL GENETICS, 5/e. © 2006 Elsevier Ltd.

This topic: MITOMAP > WebHome > NuclearGenesNonStructural
Topic revision: 17 Nov 2015, UnknownUser
This site is powered by FoswikiCopyright © by the contributing authors. All material on this collaboration platform is the property of the contributing authors.
Ideas, requests, problems regarding Foswiki? Send feedback