Reported Mitochondrial DNA Polypeptide Gene Disease Mutations, Non-LHON

Last update: March 2012

Panel A: The Top Pathogenic mtDNA Polypeptide Missense Mutations, Non-LHON

Syndromes Locus Disease Allele Nt change AA change Ho He References
DYSTONIA/LEIGH SYNDROME
Leigh syndromeMTATP6LS / NARPT8993CT-CL156P-+(A20)
Leigh syndromeMTATP6NARPT8993GT-GL156R-+(A21,A22)
Leigh syndromeMTATP6LST9176GT-GL217R++(A15)
Leigh syndromeMTATP6LS/FBSNT9176CT-CL217P++(A1,A18)
Leigh syndrome/MTATP6LS/Ataxia/ NARP-like diseaseT9185CT-CL220P++(A3)
Leigh syndromeMTND3LST10158CT-CS34P++(A4,A6,A9)
Leigh syndromeMTND3LS / LS-like Disease / ESOCT10191CT-CS45P-+(A14)
Leigh syndromeMTND3LS / Dystonia / StrokeG10197AG-AA-T++(A2,A5)
Leigh syndromeMTND4LSC11777AC-AR340S-+(A7,A8)
Leigh syndromeMTND5LST12706CT-CF124L-+(A12)
Dystonia/Leigh syndromeMTND6LDYT/LS G14459AG-AA72V++(A16,A19)
Dystonia/Leigh syndromeMTND6LS/Dystonia/AtaxiaT14487CT-CM63V-+(A10,A11)
ENCEPHALOMYOPATHY
Encephalomyopathy, MELASMTND1MELAS/LSG3697AG-AG131S-+(A5)
Encephalomyopathy, MELASMTND5MELAS/LSG13513AG-AD393N-+(A17)
Encephalomyopathy, MELASMTND5MELASA13514GA-GD393G-+(A13)


Panel B: Representative Reported Pathogenic Polypeptide Mutations, non-LHON for various phenotypic presentations selected from over 250 reported variants. Additional reports are here.

Syndromes Locus Disease Allele Nucleotide Change AA Change Ho He Status References
DYSTONIA/LEIGH SYNDROME
DystoniaMTND1Adult-Onset DystoniaA3796GA-GT164A-+Rep(11)
Leigh syndromeMTATP6LS/FBSNT9176CT-CL217P++Rep(44)
Leigh SyndromeMTATP6LST9176GT-GL217R-+Rep(21)
Leigh SyndromeMTATP6LST9185CT-CL220P-+Rep(3)
Leigh SyndromeMTATP6LST9191CT-CL222P-+Rep(3)
Leigh SyndromeMTCO3LS-likeC9537insCC-CCQ111frameshift+-Rep(24)
ENCEPHALOMYOPATHY
Encephalomyopathy, MELASMTND1MELAST3308CT-CM1T-+Rep(39)
Encephalomyopathy, MELASMTND1MELAS/LHONG3376AG-AE24K- +Rep(1)
Encephalomyopathy, MELASMTND1MELASG3697AG-AG131S-+Rep(5)
Encephalomyopathy, MELASMTND1MELASG3946AG-AE214K++Rep(5)
Encephalomyopathy, MELASMTND1MELAST3949CT-CY215H-+Rep(5)
Encephalomyopathy, MELASMTND4MELASA11084GA-GT109A++P.M.(48,50)
Encephalomyopathy, MELASMTND5MELASA12770GA-GE145G-+Rep(9)
Encephalomyopathy, MELASMTND5MELAS/LHON/ LS overlap syndromeA13045CA-CM237L-+Rep(9)
Encephalomyopathy, MELASMTND5MELAS/LS A13084TA-TS250C-+Rep(8)
Encephalomyopathy, MELASMTND6MELASG14453AG-AA74V-+Rep(17)
Encephalomyopathy, MELASMTCYBMELAS/PD14787del4TTAA-delI14frameshift-+Rep(30)
Encephalomyopathy, EpilepsyMTCO1Therapy-resistant EpilepsyC6489AC-AL196I-+Rep(14)
Encephalomyopathy, Multisystem DisorderMTCO1Multisystem DisorderG6930AG-AG343Ter-+Rep(28)
Encephalomyopathy, Multisystem DisorderMTCOIMyopathy and Cortical Lesions6015del5Del 5 bpFrameshift, 42 peptide+Rep(35)
EncephalomyopathyMTCO2EncephalomyopathyT7587CT-CM1T-+Rep(29)
Encephalomyopathy, Multisystem DisorderMTCO2Multisystem DisorderG7896AG-AW104Ter-+Rep(15)
Encephalomyopathy, Lactic AcidosisMTCO2Lactic Acidosis8042del2AT-delM153Ter-+Rep(19)
EncephalomyopathyMTCO3EncephalomyopathyG9952AG-AW248Ter-+Rep(36)
Encephalomyopathy, MELASMTCO3MELAS/PEM/ NAIONT9957CT-CF251L-+Rep(43,47)
Encephalomyopathy, Lactic AcidosisMTATP6Lactic Acidosis/ Seizures9205del2TA-delTer227M+-Rep(12)
Encephalomyopathy, Multisystem DisorderMTCYBMultisystem DisorderA15579GA-GY278C-+Rep(18)
Encephalomyopathy, Septo-Optic DysplasiaMTCYBSepto-Optic DysplasiaT14849CT-CS35P-+Rep(13)
MITOCHONDRIAL MYOPATHY
MM, Exercise IntoleranceMTCYBEXITG14846AG-AG34S-+Rep(26)
Mitochondrial MyopathyMTCYBMMG15059AG-AG190Ter-+Rep(25)
MM, Exercise IntoleranceMTCYBEXITG15084AG-AW113Ter-+Rep(26)
MM, Exercise IntoleranceMTCYBEXITG15150AG-AW135Ter-+Rep(16)
MM, Exercise IntoleranceMTCYBEXITG15168AG-AW141Ter-+Rep(26)
MM, Exercise IntoleranceMTCYBEXITT15197CT-CS151P-+Rep(16)
MM, Exercise IntoleranceMTCYBEXIT/EncephalomyopathyG15242AG-AG166Ter-+Rep(23,37)
MM, Exercise IntoleranceMTCYBEXITG15497AG-AG251S+-Rep(7)
MM, Exercise IntoleranceMTCYBEXIT15498del2424 bp deletion-251GDPDNYTL-del258-+Rep(26)
MM, Exercise IntoleranceMTCYBEXITG15615AG-AG290D-+Rep(41)
MM, Exercise IntoleranceMTCYBEXITG15723AG-AW326Ter-+Rep(26)
Mitochondrial MyopathyMTCYBMMG15762AG-AG339E-+Rep(34)
MM, CPEOMTND4CPEOT11232CT-CL140P-+Rep(10)
MM, Exercise IntoleranceMTND4EXITG11832AG-AW358Ter-+Rep(27)
MM, Exercise IntoleranceMTCO1EXIT/MyoglobinuriaG5920AG-AW6Ter-+Rep(22)
Mitochondrial MyopathyMTCO1MM & RhabdomyolysisG6708AG-AG269Ter-+Rep(2)
Mitochondrial MyopathyMTCO2MMT7671AT-AM29K-+Rep(32)
MM, Exercise IntoleranceMTCO2EXIT/RhabdomyolysisT7989CT-CL135P-+Rep(6)
Mitochondrial MyopathyMTCO3Myopathy and Myoglobinuria9487del15Del 15 bpRemoved 5 aa+Rep(42,45)
HYPERTROPHIC CARDIOMYOPATHY
Hypertrophic CardiomyopathyMTCYBHCMG15243AG-AG166E-+Rep(33)
Hypertrophic CardiomyopathyMTCYBHCMG15498AG-AG251D-+Rep(20)
DEAFNESS/SENSORINEURAL HEARING LOSS
DeafnessMTCO1DEAFA7443GA-GTer514G+-Rep(31)
DeafnessMTCO1DEAFA7445CA-CTer514S+-Rep(31)
Deafness, Sensory Neural Hearing LossMTCO1SNHL/LHONG7444AG-ATer514K+-Rep(31)
Deafness, Sensory Neural Hearing LossMTCO2SNHLA8108GA-GI175V+-Rep(4)
Deafness, Sensory Neural Hearing LossMTND6SNHLC14340TC-TV112M+-Rep(4)
HYPERTROPHIC CARDIOMYOPATHY
Diabetes MellitusMTND4DMA12026GA-GI423V+-Rep(38)
ALZHEIMER AND PARKINSON DISEASES
Alzheimer & Parkinson DiseaseMTND1ADPDA3397GA-GM31V+-Rep(49,53)
Alzheimer & Parkinson DiseaseMTND2ADG5460AG-AA331T++P.M.(46,51,52)
Alzheimer & Parkinson DiseaseMTND2ADG5460TG-TA331S++Rep(46,51,52)
HYPERTROPHIC CARDIOMYOPATHY
Idiopathic Sideroblastic AnemiaMTCO1SIDAT6721CT-CM273T-+Rep(40)
Idiopathic Sideroblastic AnemiaMTCO1SIDAT6742CT-CI280T-+Rep(40)

Abbreviations AD = Alzheimer disease; ADPD = Alzheimer plus Parkinson disease; CPEO = chronic progressive ophthalmoplegia; DEAF = deafness, sensorineural hearing loss; ESOC = Epilepsy, Strokes, Optic atrophy, and Cognitive decline; EXIT: Exercise Intolerance; FBSN = Familial Bilateral Striatal Necrosis; HCM = Hypertrophic Cardiomyopathy; MM = Mitochondrial Myopathy; MERRF = Myoclonic Epilepsy and Ragged Red Fiber Disease; MELAS = Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes; NAION = Nonarteritic Anterior Ischemic Optic Neuropathy; NARP = Neurogenic Muscle Weakness, Ataxia, and Retinitis Pigmentosa; NIDDM = Non-Insulin Dependent Diabetes Mellitus; PEM = Progressive Encephalopathy; PEO = Progressive External Ophthalmoplegia; PD = Parkinson Disease; SNHL = Sensory Neural Hearing Loss; SIDA: Sideroblastic Anemia. Ho = homoplasmic; He = heteroplasmic; Rep = Reported/provisional mutations that have been reported one or a few times in associated with disease but are not confirmed as pathogenic; P.M. = (point mutation/polymorphism) status indicates that some published reports have determined the mutation to be a non-pathogenic population variant.

References, Panel A

A1. Verny, C., Guegen, N., Desquiret, V., Chevrollier, A., Prundean, A., Dubas, F., Cassereau, J., Ferre, M., Amati-Bonneau, P., Bonneau, D., Reynier, P. and Procaccio, V. (2011). "Hereditary spastic paraplegia-like disorder due to a mitochondrial ATP6 gene point mutation". Mitochondrion 11(1):70-75.

A2. Sarzi, E., Brown, M., Lebon, S., Chretien, D., Munnich, A., Rotig, A. and Procaccio, V. (2007). "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 143A(1):33-41.

A3. Moslemi, A. R., Darin, N., Tulinius, M., Oldfors, A. and Holme, E. (2005). "Two new mutations in the MTATP6 gene associated with Leigh syndrome". Neuropediatrics 36(5):314-318.

A4. Crimi, M., Papadimitriou, A., Galbiati, S., Palamidou, P., Fortunato, F., Bordoni, A., Papandreou, U., Papadimitriou, D., Hadjigeorgiou, G. M., Drogari, E., Bresolin, N. and Comi, G. P. (2004). "A new mitochondrial DNA mutation in ND3 gene causing severe Leigh Syndrome with early lethality". Pediatric Research 55(5):842-846.

A5. Kirby, D. M., McFarland, R., Ohtake, A., Dunning, C., Ryan, M. T., Wilson, C., Ketteridge, D., Turnbull, D. M., Thorburn, D. R. and Taylor, R. W. (2004). "Mutations of the mitochondrial ND1 gene as a cause of MELAS". Journal of Medical Genetics 41(10):784-789.

A6. McFarland, R., Kirby, D. M., Fowler, K. J., Ohtake, A., Ryan, M. T., Amor, D. J., Fletcher, J. M., Dixon, J. W., Collins, F. A., Turnbull, D. M., Taylor, R. W. and Thorburn, D. R. (2004). "De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency". Annals of Neurology 55(1):58-64.

A7. Deschauer, M., Bamberg, C., Claus, D., Zierz, S., Turnbull, D. M. and Taylor, R. W. (2003). "Late-onset encephalopathy associated with a C11777A mutation of mitochondrial DNA". Neurology 60(8):1357-1359.

A8. Komaki, H., Akanuma, J., Iwata, H., Takahashi, T., Mashima, Y., Nonaka, I. and Goto, Y. (2003). "A novel mtDNA C11777A mutation in Leigh syndrome". Mitochondrion 2(4):293-304.

A9. Lebon, S., Chol, M., Benit, P., Mugnier, C., Chretien, D., Giurgea, I., Kern, I., Girardin, E., Hertz-Pannier, L., de Lonlay, P., Rotig, A., Rustin, P. and Munnich, A. (2003). "Recurrent de novo mitochondrial DNA mutations in respiratory chain deficiency". Journal of Medical Genetics 40(12):896-899.

A10. Solano, A., Roig, M., Vives-Bauza, C., Hernandez-Pena, J., Garcia-Arumi, E., Playan, A., Lopez-Perez, M. J., Andreu, A. L. and Montoya, J. (2003). "Bilateral striatal necrosis associated with a novel mutation in the mitochondrial ND6 gene". Annals of Neurology 54(4):527-530.

A11. Ugalde, C., Triepels, R. H., Coenen, M. J., van den Heuvel, L. P., Smeets, R., Uusimaa, J., Briones, P., Campistol, J., Majamaa, K., Smeitink, J. A. and Nijtmans, L. G. (2003). "Impaired complex I assembly in a Leigh syndrome patient with a novel missense mutation in the ND6 gene". Annals of Neurology 54(5):665-669.

A12. Taylor, R. W., Morris, A. A., Hutchinson, M. and Turnbull, D. M. (2002). "Leigh disease associated with a novel mitochondrial DNA ND5 mutation". European Journal of Human Genetics 10(2):141-144.

A13. Corona, P., Antozzi, C., Carrara, F., D'Incerti, L., Lamantea, E., Tiranti, V. and Zeviani, M. (2001). "A novel mtDNA mutation in the ND5 subunit of complex I in two MELAS patients". Annals of Neurology 49(1):106-110.

A14. Taylor, R. W., Singh-Kler, R., Hayes, C. M., Smith, P. E. and Turnbull, D. M. (2001). "Progressive mitochondrial disease resulting from a novel missense mutation in the mitochondrial DNA ND3 gene". Annals of Neurology 50(1):104-107.

A15. Carrozzo, R., Murray, J., Santorelli, F. M. and Capaldi, R. A. (2000). "The T9176G mutation of human mtDNA gives a fully assembled but inactive ATP synthase when modeled in Escherichia coli". FEBS Letters 486(3):297-299.

A16. Kirby, D. M., Kahler, S. G., Freckmann, M. L., Reddihough, D. and Thorburn, D. R. (2000). "Leigh disease caused by the mitochondrial DNA G14459A mutation in unrelated families". Annals of Neurology 48(1):102-104.

A17. Santorelli, F. M., Tanji, K., Kulikova, R., Shanske, S., Vilarinho, L., Hays, A. P. and DiMauro, S. (1997). "Identification of a novel mutation in the mtDNA ND5 gene associated with MELAS". Biochemical and Biophysical Research Communications 238(2):326-328.

A18. Thyagarajan, D., Shanske, S., Vazquez-Memije, M., De Vivo, D. and DiMauro, S. (1995). "A novel mitochondrial ATPase 6 point mutation in familial bilateral striatal necrosis". Annals of Neurology 38(3):468-472.

A19. Jun, A. S., Brown, M. D. and Wallace, D. C. (1994). "A mitochondrial DNA mutation at np 14459 of the ND6 gene associated with maternally inherited Leber's hereditary optic neuropathy and dystonia". Proceedings of the National Academy of Sciences of the United States of America 91(13):6206-6210.

A20. De Vries, D. D., Van Engelen, B. G., Gabreels, F. J., Ruitenbeek, W. and Van Oost, B. A. (1993). "A second missense mutation in the mitochondrial ATPase 6 gene in Leigh's syndrome". Annals of Neurology 34(3):410-412.

A21. Harding, A. E., Holt, I. J., Sweeney, M. G., Brockington, M. and Davis, M. B. (1992). "Prenatal diagnosis of mitochondrial DNA8993 T-G disease". American Journal of Human Genetics 50(3):629-633.

A22. Holt, I. J., Harding, A. E., Petty, R. K. and Morgan-Hughes, J. A. (1990). "A new mitochondrial disease associated with mitochondrial DNA heteroplasmy". American Journal of Human Genetics 46(3):428-433.

 

References, Panel B

1. Blakely, E. L., de Silva, R., King, A., Schwarzer, V., Harrower, T., Dawidek, G., Turnbull, D. M. and Taylor, R. W. (2005). "LHON/MELAS overlap syndrome associated with a mitochondrial MTND1 gene mutation". European Journal of Human Genetics 13(5):623-627.

2. Kollberg, G., Moslemi, A. R., Lindberg, C., Holme, E. and Oldfors, A. (2005). "Mitochondrial myopathy and rhabdomyolysis associated with a novel nonsense mutation in the gene encoding cytochrome c oxidase subunit I". Journal of Neuropathology and Experimental Neurology 64(2):123-128.

3. Moslemi, A. R., Darin, N., Tulinius, M., Oldfors, A. and Holme, E. (2005). "Two new mutations in the MTATP6 gene associated with Leigh syndrome". Neuropediatrics 36(5):314-318.

4. Wang, Q., Li, R., Zhao, H., Peters, J. L., Liu, Q., Yang, L., Han, D., Greinwald, J. H., Jr., Young, W. Y. and Guan, M. X. (2005). "Clinical and molecular characterization of a Chinese patient with auditory neuropathy associated with mitochondrial 12S rRNA T1095C mutation". American Journal of Medical Genetics 133A(1):27-30.

5. Kirby, D. M., McFarland, R., Ohtake, A., Dunning, C., Ryan, M. T., Wilson, C., Ketteridge, D., Turnbull, D. M., Thorburn, D. R. and Taylor, R. W. (2004). "Mutations of the mitochondrial ND1 gene as a cause of MELAS". Journal of Medical Genetics 41(10):784-789.

6. McFarland, R., Taylor, R. W., Chinnery, P. F., Howell, N. and Turnbull, D. M. (2004). "A novel sporadic mutation in cytochrome c oxidase subunit II as a cause of rhabdomyolysis". Neuromuscular Disorders 14(2):162-166.

7. Tarnopolsky, M. A., Simon, D. K., Roy, B. D., Chorneyko, K., Lowther, S. A., Johns, D. R., Sandhu, J. K., Li, Y. and Sikorska, M. (2004). "Attenuation of free radical production and paracrystalline inclusions by creatine supplementation in a patient with a novel cytochrome b mutation". Muscle and Nerve 29(4):537-547.

8. Crimi, M., Galbiati, S., Moroni, I., Bordoni, A., Perini, M. P., Lamantea, E., Sciacco, M., Zeviani, M., Biunno, I., Moggio, M., Scarlato, G. and Comi, G. P. (2003). "A missense mutation in the mitochondrial ND5 gene associated with a Leigh-MELAS overlap syndrome". Neurology 60(11):1857-1861.

9. Liolitsa, D., Rahman, S., Benton, S., Carr, L. J. and Hanna, M. G. (2003). "Is the mitochondrial complex I ND5 gene a hot-spot for MELAS causing mutations?". Annals of Neurology 53(1):128-132.

10. Pulkes, T., Liolitsa, D., Nelson, I. P. and Hanna, M. G. (2003). "Classical mitochondrial phenotypes without mtDNA mutations: The possible role of nuclear genes". Neurology 61(8):1144-1147.

11. Simon, D. K., Friedman, J., Breakefield, X. O., Jankovic, J., Brin, M. F., Provias, J., Bressman, S. B., Charness, M. E., Tarsy, D., Johns, D. R. and Tarnopolsky, M. A. (2003). "A heteroplasmic mitochondrial complex I gene mutation in adult-onset dystonia". Neurogenetics 4(4):199-205.

12. Temperley, R. J., Seneca, S. H., Tonska, K., Bartnik, E., Bindoff, L. A., Lightowlers, R. N. and Chrzanowska-Lightowlers, Z. M. (2003). "Investigation of a pathogenic mtDNA microdeletion reveals a translation-dependent deadenylation decay pathway in human mitochondria". Human Molecular Genetics 12(18):2341-2348.

13. Schuelke, M., Krude, H., Finckh, B., Mayatepek, E., Janssen, A., Schmelz, M., Trefz, F., Trijbels, F. and Smeitink, J. (2002). "Septo-optic dysplasia associated with a new mitochondrial cytochrome b mutation". Annals of Neurology 51(3):388-392.

14. Varlamov, D. A., Kudin, A. P., Vielhaber, S., Schroder, R., Sassen, R., Becker, A., Kunz, D., Haug, K., Rebstock, J., Heils, A., Elger, C. E. and Kunz, W. S. (2002). "Metabolic consequences of a novel missense mutation of the mtDNA CO I gene". Human Molecular Genetics 11(16):1797-1805.

15. Campos, Y., Garcia-Redondo, A., Fernandez-Moreno, M. A., Martinez-Pardo, M., Goda, G., Rubio, J. C., Martin, M. A., del Hoyo, P., Cabello, A., Bornstein, B., Garesse, R. and Arenas, J. (2001). "Early-onset multisystem mitochondrial disorder caused by a nonsense mutation in the mitochondrial DNA cytochrome C oxidase II gene". Annals of Neurology 50(3):409-413.

16. Legros, F., Chatzoglou, E., Frachon, P., Ogier De Baulny, H., Laforet, P., Jardel, C., Godinot, C. and Lombes, A. (2001). "Functional characterization of novel mutations in the human cytochrome b gene". European Journal of Human Genetics 9(7):510-518.

17. Ravn, K., Wibrand, F., Hansen, F. J., Horn, N., Rosenberg, T. and Schwartz, M. (2001). "An mtDNA mutation, 14453G-A, in the NADH dehydrogenase subunit 6 associated with severe MELAS syndrome". European Journal of Human Genetics 9(10):805-809.

18. Wibrand, F., Ravn, K., Schwartz, M., Rosenberg, T., Horn, N. and Vissing, J. (2001). "Multisystem disorder associated with a missense mutation in the mitochondrial cytochrome b gene". Annals of Neurology 50(4):540-543.

19. Wong, L. J., Dai, P., Tan, D., Lipson, M., Grix, A., Sifry-Platt, M., Gropman, A. and Chen, T. J. (2001). "Severe lactic acidosis caused by a novel frame-shift mutation in mitochondrial-encoded cytochrome c oxidase subunit II". American Journal of Medical Genetics 102(1):95-99.

20. Andreu, A. L., Checcarelli, N., Iwata, S., Shanske, S. and DiMauro, S. (2000). "A missense mutation in the mitochondrial cytochrome b gene in a revisited case with histiocytoid cardiomyopathy". Pediatric Research 48(3):311-314.

21. Carrozzo, R., Murray, J., Santorelli, F. M. and Capaldi, R. A. (2000). "The T9176G mutation of human mtDNA gives a fully assembled but inactive ATP synthase when modeled in Escherichia coli". FEBS Letters 486(3):297-299.

22. Karadimas, C. L., Greenstein, P., Sue, C. M., Joseph, J. T., Tanji, K., Haller, R. G., Taivassalo, T., Davidson, M. M., Shanske, S., Bonilla, E. and DiMauro, S. (2000). "Recurrent myoglobinuria due to a nonsense mutation in the COX I gene of mitochondrial DNA". Neurology 55(5):644-649.

23. Keightley, J. A., Anitori, R., Burton, M. D., Quan, F., Buist, N. R. and Kennaway, N. G. (2000). "Mitochondrial encephalomyopathy and complex III deficiency associated with a stop-codon mutation in the cytochrome b gene". American Journal of Human Genetics 67(6):1400-1410.

24. Tiranti, V., Corona, P., Greco, M., Taanman, J. W., Carrara, F., Lamantea, E., Nijtmans, L., Uziel, G. and Zeviani, M. (2000). "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". Human Molecular Genetics 9(18):2733-2742.

25. Andreu, A. L., Bruno, C., Dunne, T. C., Tanji, K., Shanske, S., Sue, C. M., Krishna, S., Hadjigeorgiou, G. M., Shtilbans, A., Bonilla, E. and DiMauro, S. (1999). "A nonsense mutation (G15059A) in the cytochrome b gene in a patient with exercise intolerance and myoglobinuria". Annals of Neurology 45(1):127-130.

26. Andreu, A. L., Hanna, M. G., Reichmann, H., Bruno, C., Penn, A. S., Tanji, K., Pallotti, F., Iwata, S., Bonilla, E., Lach, B., Morgan-Hughes, J. and DiMauro, S. (1999). "Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial DNA". The New England Journal of Medicine 341(14):1037-1044.

27. Andreu, A. L., Tanji, K., Bruno, C., Hadjigeorgiou, G. M., Sue, C. M., Jay, C., Ohnishi, T., Shanske, S., Bonilla, E. and DiMauro, S. (1999). "Exercise intolerance due to a nonsense mutation in the mtDNA ND4 gene". Annals of Neurology 45(6):820-823.

28. Bruno, C., Martinuzzi, A., Tang, Y., Andreu, A. L., Pallotti, F., Bonilla, E., Shanske, S., Fu, J., Sue, C. M., Angelini, C., DiMauro, S. and Manfredi, G. (1999). "A stop-codon mutation in the human mtDNA cytochrome c oxidase I gene disrupts the functional structure of complex IV". American Journal of Human Genetics 65(3):611-620.

29. Clark, K. M., Taylor, R. W., Johnson, M. A., Chinnery, P. F., Chrzanowska-Lightowlers, Z. M., Andrews, R. M., Nelson, I. P., Wood, N. W., Lamont, P. J., Hanna, M. G., Lightowlers, R. N. and Turnbull, D. M. (1999). "An mtDNA mutation in the initiation codon of the cytochrome C oxidase subunit II gene results in lower levels of the protein and a mitochondrial encephalomyopathy". American Journal of Human Genetics 64(5):1330-1339.

30. de Coo, I. F., Renier, W. O., Ruitenbeek, W., Ter Laak, H. J., Bakker, M., Schagger, H., Van Oost, B. A. and Smeets, H. J. (1999). "A 4-base pair deletion in the mitochondrial cytochrome b gene associated with parkinsonism/MELAS overlap syndrome". Annals of Neurology 45(1):130-133.

31. Pandya, A., Xia, X. J., Erdenetungalag, R., Amendola, M., Landa, B., Radnaabazar, J., Dangaasuren, B., Van Tuyle, G. and Nance, W. E. (1999). "Heterogenous point mutations in the mitochondrial tRNA Ser(UCN) precursor coexisting with the A1555G mutation in deaf students from Mongolia". American Journal of Human Genetics 65(6):1803-1806.

32. Rahman, S., Taanman, J. W., Cooper, J. M., Nelson, I., Hargreaves, I., Meunier, B., Hanna, M. G., Garcia, J. J., Capaldi, R. A., Lake, B. D., Leonard, J. V. and Schapira, A. H. (1999). "A missense mutation of cytochrome oxidase subunit II causes defective assembly and myopathy". American Journal of Human Genetics 65(4):1030-1039.

33. Valnot, I., Kassis, J., Chretien, D., de Lonlay, P., Parfait, B., Munnich, A., Kachaner, J., Rustin, P. and Rotig, A. (1999). "A mitochondrial cytochrome b mutation but no mutations of nuclearly encoded subunits in ubiquinol cytochrome c reductase (complex III) deficiency". Human Genetics 104(6):460-466.

34. Andreu, A. L., Bruno, C., Shanske, S., Shtilbans, A., Hirano, M., Krishna, S., Hayward, L., Systrom, D. S., Brown, R. H., Jr. and DiMauro, S. (1998). "Missense mutation in the mtDNA cytochrome b gene in a patient with myopathy". Neurology 51(5):1444-1447.

35. Comi, G. P., Bordoni, A., Salani, S., Franceschina, L., Sciacco, M., Prelle, A., Fortunato, F., Zeviani, M., Napoli, L., Bresolin, N., Moggio, M., Ausenda, C. D., Taanman, J. W. and Scarlato, G. (1998). "Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease". Annals of Neurology 43(1):110-116.

36. Hanna, M. G., Nelson, I. P., Rahman, S., Lane, R. J., Land, J., Heales, S., Cooper, M. J., Schapira, A. H., Morgan-Hughes, J. A. and Wood, N. W. (1998). "Cytochrome c oxidase deficiency associated with the first stop-codon point mutation in human mtDNA". American Journal of Human Genetics 63(1):29-36.

37. Kennaway, N. G., Keightley, J. A., Burton, M. D., Quan, F., Libby, B. D. and Buist, N. M. R. (1998). Mitochondrial encephalomyopathy associated with a nonsense mutation in the cytochrome b (Abstract). In: UCSD Mitochondrial Medicine Conference. San Diego, California, USA. February 19-21, 1998.". Molecular Genetics and Metabolism 63(1):49.

38. Tawata, M., Ohtaka, M., Iwase, E., Ikegishi, Y., Aida, K. and Onaya, T. (1998). "New mitochondrial DNA homoplasmic mutations associated with Japanese patients with type 2 diabetes". Diabetes 47(2):276-277.

39. Campos, Y., Martin, M. A., Rubio, J. C., Gutierrez del Olmo, M. C., Cabello, A. and Arenas, J. (1997). "Bilateral striatal necrosis and MELAS associated with a new T3308C mutation in the mitochondrial ND1 gene". Biochemical and Biophysical Research Communications 238(2):323-325.

40. Gattermann, N., Retzlaff, S., Wang, Y. L., Hofhaus, G., Heinisch, J., Aul, C. and Schneider, W. (1997). "Heteroplasmic point mutations of mitochondrial DNA affecting subunit I of cytochrome c oxidase in two patients with acquired idiopathic sideroblastic anemia". Blood 90(12):4961-4972.

41. Dumoulin, R., Sagnol, I., Ferlin, T., Bozon, D., Stepien, G. and Mousson, B. (1996). A novel gly290asp mitochondrial cytochrome b mutation linked to a complex III deficiency in progressive exercise intolerance". Molecular and Cellular Probes 10(5):389-391.

42. Kennaway, N. G., Keightley, J. A., Burton, M., Hoffbuhr, K. and Buist, N. R. M. (1995). "Single fiber analysis of muscle from a patient with a microdeletion in the gene for cytochrome c oxidase (COX) subunit III. (Abstract FC084)." EUROMIT III, The Third International Meeting on Human Mitochondrial Pathology, Chantilly, France:64.

43. Manfredi, G., Schon, E. A., Moraes, C. T., Bonilla, E., Berry, G. T., Sladky, J. T. and DiMauro, S. (1995). "A new mutation associated with MELAS is located in a mitochondrial DNA polypeptide-coding gene". Neuromuscular Disorders 5(5):391-398.

44. Thyagarajan, D., Shanske, S., Vazquez-Memije, M., De Vivo, D. and DiMauro, S. (1995). "A novel mitochondrial ATPase 6 point mutation in familial bilateral striatal necrosis". Annals of Neurology 38(3):468-472.

45. Kennaway, N. G., Burton, M. D., Hall, R. E., Johnston, W. S. W., Keightley, J. A., Salas, V. M. and Tindle, N. A. (1994). Mitochondrial myopathy and cytochrome c oxidase (COX) deficiency associated with a 15 bp deletion in the gene for COX subunit III. (Abstract 827)". Neurology 44 Suppl 2(4):A335.

46. Kosel, S., Egensperger, R., Mehraein, P. and Graeber, M. B. (1994). "No association of mutations at nucleotide 5460 of mitochondrial NADH dehydrogenase with Alzheimer's disease". Biochemical and Biophysical Research Communications 203(2):745-749.

47. Manfredi, G., Bonilla, E., Schon, E. A., DiMauro, S. and Moraes, C. (1994). "A mitochondrial DNA missense mutation in the cytochrome oxidase subunit III gene associated with a progressive encephalopathy." Miami Short Reports 4:17.

48. Sakuta, R., Goto, Y., Nonaka, I. and Horai, S. (1993). "An A-to-G transition at nucleotide pair 11084 in the ND4 gene may be an mtDNA polymorphism". American Journal of Human Genetics 53(4):964-965.

49. Shoffner, J. M., Brown, M. D., Torroni, A., Lott, M. T., Cabell, M. R., Mirra, S. S., Beal, M. F., Yang, C., Gearing, M., Salvo, R., Watts, R. L., Juncos, J. L., Hansen, L. A., Crain, B. J., Fayad, M., Reckord, C. L. and Wallace, D. C. (1993). "Mitochondrial DNA variants observed in Alzheimer disease and Parkinson disease patients". Genomics 17(1):171-184.

50. Lertrit, P., Noer, A. S., Jean-Francois, M. J., Kapsa, R., Dennett, X., Thyagarajan, D., Lethlean, K., Byrne, E. and Marzuki, S. (1992). A new disease-related mutation for mitochondrial encephalopathy lactic acidosis and strokelike episodes (MELAS) syndrome affects the ND4 subunit of the respiratory complex I". American Journal of Human Genetics 51(3):457-468.

51. Lin, F., Lin, R., Wisniewski, H. M., Hwang, Y., Grundke-Iqbal, I., Healy-Louie, G. and Iqbal, K. (1992). "Detection of point mutations in codon 331 of mitochondrial NADH dehydrogenase subunit 2 in Alzheimer's brains". Biochemical and Biophysical Research Communications 182(1):238-246.

52. Petruzzella, V., Chen, X. and Schon, E. A. (1992). "Is a point mutation in the mitochondrial ND2 gene associated with Alzheimer's disease?". Biochemical and Biophysical Research Communications 186(1):491-497.

53. Wallace, D. C., Shoffner, J. M., Brown, M. D., Torroni, A., Lott, M. T. and Cabell, M. (1992). "Mitochondrial DNA mutations associated with Alzheimer's and Parkinson's disease." American Journal of Human Genetics 51:A30.


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.

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