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 syndrome	MTATP6	LS / NARP	T8993C	T-C	L156P	-	+	(A20)
Leigh syndrome	MTATP6	NARP	T8993G	T-G	L156R	-	+	(A21,A22)
Leigh syndrome	MTATP6	LS	T9176G	T-G	L217R	+	+	(A15)
Leigh syndrome	MTATP6	LS/FBSN	T9176C	T-C	L217P	+	+	(A1,A18)
Leigh syndrome/	MTATP6	LS/Ataxia/ NARP-like disease	T9185C	T-C	L220P	+	+	(A3)
Leigh syndrome	MTND3	LS	T10158C	T-C	S34P	+	+	(A4,A6,A9)
Leigh syndrome	MTND3	LS / LS-like Disease / ESOC	T10191C	T-C	S45P	-	+	(A14)
Leigh syndrome	MTND3	LS / Dystonia / Stroke	G10197A	G-A	A-T	+	+	(A2,A5)
Leigh syndrome	MTND4	LS	C11777A	C-A	R340S	-	+	(A7,A8)
Leigh syndrome	MTND5	LS	T12706C	T-C	F124L	-	+	(A12)
Dystonia/Leigh syndrome	MTND6	LDYT/LS	G14459A	G-A	A72V	+	+	(A16,A19)
Dystonia/Leigh syndrome	MTND6	LS/Dystonia/Ataxia	T14487C	T-C	M63V	-	+	(A10,A11)
ENCEPHALOMYOPATHY
Encephalomyopathy, MELAS	MTND1	MELAS/LS	G3697A	G-A	G131S	-	+	(A5)
Encephalomyopathy, MELAS	MTND5	MELAS/LS	G13513A	G-A	D393N	-	+	(A17)
Encephalomyopathy, MELAS	MTND5	MELAS	A13514G	A-G	D393G	-	+	(A13)

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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
Dystonia	MTND1	Adult-Onset Dystonia	A3796G	A-G	T164A	-	+	Rep	(11)
Leigh syndrome	MTATP6	LS/FBSN	T9176C	T-C	L217P	+	+	Rep	(44)
Leigh Syndrome	MTATP6	LS	T9176G	T-G	L217R	-	+	Rep	(21)
Leigh Syndrome	MTATP6	LS	T9185C	T-C	L220P	-	+	Rep	(3)
Leigh Syndrome	MTATP6	LS	T9191C	T-C	L222P	-	+	Rep	(3)
Leigh Syndrome	MTCO3	LS-like	C9537insC	C-CC	Q111frameshift	+	-	Rep	(24)
ENCEPHALOMYOPATHY
Encephalomyopathy, MELAS	MTND1	MELAS	T3308C	T-C	M1T	-	+	Rep	(39)
Encephalomyopathy, MELAS	MTND1	MELAS/LHON	G3376A	G-A	E24K	-	+	Rep	(1)
Encephalomyopathy, MELAS	MTND1	MELAS	G3697A	G-A	G131S	-	+	Rep	(5)
Encephalomyopathy, MELAS	MTND1	MELAS	G3946A	G-A	E214K	+	+	Rep	(5)
Encephalomyopathy, MELAS	MTND1	MELAS	T3949C	T-C	Y215H	-	+	Rep	(5)
Encephalomyopathy, MELAS	MTND4	MELAS	A11084G	A-G	T109A	+	+	P.M.	(48,50)
Encephalomyopathy, MELAS	MTND5	MELAS	A12770G	A-G	E145G	-	+	Rep	(9)
Encephalomyopathy, MELAS	MTND5	MELAS/LHON/ LS overlap syndrome	A13045C	A-C	M237L	-	+	Rep	(9)
Encephalomyopathy, MELAS	MTND5	MELAS/LS	A13084T	A-T	S250C	-	+	Rep	(8)
Encephalomyopathy, MELAS	MTND6	MELAS	G14453A	G-A	A74V	-	+	Rep	(17)
Encephalomyopathy, MELAS	MTCYB	MELAS/PD	14787del4	TTAA-del	I14frameshift	-	+	Rep	(30)
Encephalomyopathy, Epilepsy	MTCO1	Therapy-resistant Epilepsy	C6489A	C-A	L196I	-	+	Rep	(14)
Encephalomyopathy, Multisystem Disorder	MTCO1	Multisystem Disorder	G6930A	G-A	G343Ter	-	+	Rep	(28)
Encephalomyopathy, Multisystem Disorder	MTCOI	Myopathy and Cortical Lesions	6015del5	Del 5 bp	Frameshift, 42 peptide		+	Rep	(35)
Encephalomyopathy	MTCO2	Encephalomyopathy	T7587C	T-C	M1T	-	+	Rep	(29)
Encephalomyopathy, Multisystem Disorder	MTCO2	Multisystem Disorder	G7896A	G-A	W104Ter	-	+	Rep	(15)
Encephalomyopathy, Lactic Acidosis	MTCO2	Lactic Acidosis	8042del2	AT-del	M153Ter	-	+	Rep	(19)
Encephalomyopathy	MTCO3	Encephalomyopathy	G9952A	G-A	W248Ter	-	+	Rep	(36)
Encephalomyopathy, MELAS	MTCO3	MELAS/PEM/ NAION	T9957C	T-C	F251L	-	+	Rep	(43,47)
Encephalomyopathy, Lactic Acidosis	MTATP6	Lactic Acidosis/ Seizures	9205del2	TA-del	Ter227M	+	-	Rep	(12)
Encephalomyopathy, Multisystem Disorder	MTCYB	Multisystem Disorder	A15579G	A-G	Y278C	-	+	Rep	(18)
Encephalomyopathy, Septo-Optic Dysplasia	MTCYB	Septo-Optic Dysplasia	T14849C	T-C	S35P	-	+	Rep	(13)
MITOCHONDRIAL MYOPATHY
MM, Exercise Intolerance	MTCYB	EXIT	G14846A	G-A	G34S	-	+	Rep	(26)
Mitochondrial Myopathy	MTCYB	MM	G15059A	G-A	G190Ter	-	+	Rep	(25)
MM, Exercise Intolerance	MTCYB	EXIT	G15084A	G-A	W113Ter	-	+	Rep	(26)
MM, Exercise Intolerance	MTCYB	EXIT	G15150A	G-A	W135Ter	-	+	Rep	(16)
MM, Exercise Intolerance	MTCYB	EXIT	G15168A	G-A	W141Ter	-	+	Rep	(26)
MM, Exercise Intolerance	MTCYB	EXIT	T15197C	T-C	S151P	-	+	Rep	(16)
MM, Exercise Intolerance	MTCYB	EXIT/Encephalomyopathy	G15242A	G-A	G166Ter	-	+	Rep	(23,37)
MM, Exercise Intolerance	MTCYB	EXIT	G15497A	G-A	G251S	+	-	Rep	(7)
MM, Exercise Intolerance	MTCYB	EXIT	15498del24	24 bp deletion-	251GDPDNYTL-del258	-	+	Rep	(26)
MM, Exercise Intolerance	MTCYB	EXIT	G15615A	G-A	G290D	-	+	Rep	(41)
MM, Exercise Intolerance	MTCYB	EXIT	G15723A	G-A	W326Ter	-	+	Rep	(26)
Mitochondrial Myopathy	MTCYB	MM	G15762A	G-A	G339E	-	+	Rep	(34)
MM, CPEO	MTND4	CPEO	T11232C	T-C	L140P	-	+	Rep	(10)
MM, Exercise Intolerance	MTND4	EXIT	G11832A	G-A	W358Ter	-	+	Rep	(27)
MM, Exercise Intolerance	MTCO1	EXIT/Myoglobinuria	G5920A	G-A	W6Ter	-	+	Rep	(22)
Mitochondrial Myopathy	MTCO1	MM & Rhabdomyolysis	G6708A	G-A	G269Ter	-	+	Rep	(2)
Mitochondrial Myopathy	MTCO2	MM	T7671A	T-A	M29K	-	+	Rep	(32)
MM, Exercise Intolerance	MTCO2	EXIT/Rhabdomyolysis	T7989C	T-C	L135P	-	+	Rep	(6)
Mitochondrial Myopathy	MTCO3	Myopathy and Myoglobinuria	9487del15	Del 15 bp	Removed 5 aa		+	Rep	(42,45)
HYPERTROPHIC CARDIOMYOPATHY
Hypertrophic Cardiomyopathy	MTCYB	HCM	G15243A	G-A	G166E	-	+	Rep	(33)
Hypertrophic Cardiomyopathy	MTCYB	HCM	G15498A	G-A	G251D	-	+	Rep	(20)
DEAFNESS/SENSORINEURAL HEARING LOSS
Deafness	MTCO1	DEAF	A7443G	A-G	Ter514G	+	-	Rep	(31)
Deafness	MTCO1	DEAF	A7445C	A-C	Ter514S	+	-	Rep	(31)
Deafness, Sensory Neural Hearing Loss	MTCO1	SNHL/LHON	G7444A	G-A	Ter514K	+	-	Rep	(31)
Deafness, Sensory Neural Hearing Loss	MTCO2	SNHL	A8108G	A-G	I175V	+	-	Rep	(4)
Deafness, Sensory Neural Hearing Loss	MTND6	SNHL	C14340T	C-T	V112M	+	-	Rep	(4)
HYPERTROPHIC CARDIOMYOPATHY
Diabetes Mellitus	MTND4	DM	A12026G	A-G	I423V	+	-	Rep	(38)
ALZHEIMER AND PARKINSON DISEASES
Alzheimer & Parkinson Disease	MTND1	ADPD	A3397G	A-G	M31V	+	-	Rep	(49,53)
Alzheimer & Parkinson Disease	MTND2	AD	G5460A	G-A	A331T	+	+	P.M.	(46,51,52)
Alzheimer & Parkinson Disease	MTND2	AD	G5460T	G-T	A331S	+	+	Rep	(46,51,52)
HYPERTROPHIC CARDIOMYOPATHY
Idiopathic Sideroblastic Anemia	MTCO1	SIDA	T6721C	T-C	M273T	-	+	Rep	(40)
Idiopathic Sideroblastic Anemia	MTCO1	SIDA	T6742C	T-C	I280T	-	+	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.

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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.