Non-Structural Nuclear Genes for Mitochondrial Disease

Last update: January 2018

Complex	Name	OMIM	Function	Chromosome	Inheritance	Clinical Phenotype	References
Assembly
Complex I	NDUFAF1(CIA30)	606934	Assembly	15q13.3	AR	Cardioencephalomyopathy	[i]
	NDUFAF2 (B17.2L)	609653	Assembly	5q12.1	AR	Early onset progressive encephalopathy	[ii]
	NDUFAF3	612911	Assembly	3p21.31	AR	Neonatal encephalopathy	[iii]
	NDUFAF4 (HRPAP2)	611776	Assembly	6q16.1	AR	Infantile encephalopathy	[iv]
	NDUFAF5 (C20orf7)	612360	Assembly	20p12.1	AR	LS	[v]
	NDUFAF6	612392	Assembly	8q22.1	AR	LS	[vi]
	NUBPL	613621	Assembly	14q12	AR	Encephalomyopathy	[vii]
	FOXRED1	613622	Assembly	11q24.2	AR	LS	[viii]
	ACAD9	611103	Assembly and activity	3q26	AR	Hypertrophic cardiopathy encephalopathy	[ix]
Complex II	SDHAF1	612848	Assembly	19q12-q13.2	AR	Leukoencephalopathy	[x]
	SDHAF2	613019	Assembly	11q12.2	AD	Autosomal dominant paraganglioma type 2	[xi]
Complex III	BCS1L	603647	Assembly	2q33	AR	Encephalopathy, hepatic failure and tubulopathy, LS, GRACILE syndrome, Bjornstad Syndrome	[xii]
	UQCC2	614461	Assembly	6p21.31	AR	lactic acidosis and renal tubular dysfunction	[xiii]
	UQCC3	616097	Assembly	11q12.3	AR	lactic acidosis, hypoglycemia, hypotonia	[xiv]
Complex IV	SURF1	185620	Assembly	9q34	AR	LS	[xv]
	SCO1	603644	Copper transport	17p13-p12	AR	Neonatal hepatic failure and encephalopathy	[xvi]
	SCO2	604272	Copper transport	22q13	AR	Neonatal Cardioencephalomyopathy	[xvii]
	COX10	602125	Heme A farnesyltransferase	17p12-p11.2	AR	Neonatal tubulopathy and encephalopathy, LS, cardiomyopathy	[xviii]
	COX14 (C12orf62)	614478	COX assembly	12q13.12	AR	Neonatal lactic acidosis	[xix]
	COX15	603646	Heme A synthesis	10q24	AR	Early-onset hypertrophic cardiomyopathy, LS	[xx]
	COX20	614698	Assembly	1q44	AR	Ataxia, muscle hypotonia	[xxi]
	COA3	614775	Assembly	17q21.2	AR	Neuropathy, exercise intolerance	[xxii]
	COA5	613920	Assembly	2q11.2	AR	Cardioencephalomyopathy	[xxiii]
	COA6	614772	Assembly	1q42.2	AR	Cardioencephalomyopathy	[xxiv]
	LRPPRC	220111 607544	Assembly	2p21-p16	AR	French-Canadian LS	[xxv]
	FASTKD2	612322	Role in apoptosis	2q33.3	AR	Encephalomyopathy	[xxvi]
	TACO1	612958	translational activator of COX1	17q22-q24.2	AR	LS	[xxvii]
Complex V	ATPAF2	608918	Assembly	17p11.2	AR	Early-onset encephalopathy, Lactic acidosis	[xxviii]
	TMEM70	604273 612418	Assembly	8q21.11	AR	Neonatal encephalopathy, cardiomyopathy	[xxix]
MtDNA Maintenance	POLG (PEOA1)	174763	Polymerase gamma mtDNA replication	15q25	AD-AR	Alpers syndrome, AD-PEO and AR-PEO, male infertility, SANDO* syndrome, SCAE*	[xxx]
	POLG2 (PEOA4)	610131	catalytic subunit of DNA polymerase gamma	17q23-q24	AD	AD-PEO	[xxxi]
	ANT1 (PEOA2)	609283	Adenine nucleotide translocator isoform 1	4q35	AD-AR	AD-PEO, multiple mtDNA deletions	[xxxii]
	MPV17	137960	regulation of mtDNA copy number	2p23-p21	AR	Hepatocerebral MDDS	[xxxiii]
	OPA1	165500	Dynamin-related protein	3q28-q29	AD	AD-Optic Atrophy, Multiple deletions	[xxxiv]
	MFN2	609260	Mitofusin Mitochondrial fusion	1p36-p35	AD	Charcot-Marie-Tooth disease-2A2 (CMT2A2) Multiple deletions	[xxxv]
	C10ORF (PEOA3)	609286	Twinkle helicase	10q24	AD	AD-PEO, SANDO syndrome	[xxxvi]
	TYMP (ECGF1)	603041	Thymidine phosphorylase	22q13.32-qter	AR	MNGIE, mtDNA depletion	[xxxvii]
	DGUOK	601465	Deoxyguanosine kinase Mitochondrial dNTP pool maintenance	2p13	AR	Hepatocerebral mtDNA depletion syndrome	[xxxviii]
	RRM2B (PEOA5)	604712	ribonucleotide reductase M2 B dNTP pool	8q23.1	AR	Encephalomyopathic Renal tubulopathy MNGIE, AD-PEO	[xxxix]
	SUCLA2	603921	succinate-CoA ligase, ADP-forming, beta subunit	13q12.2-q13	AR	Encephalomyopathy with methylmalonic aciduria	[xl]
	SUCLG1	611224	succinate-CoA ligase, alpha subunit	2p11.2	AR	Encephalomyopathy with methylmalonic aciduria	[xli]
	TK2	188250	Thymidine kinase Mitochondrial dNTP pool maintenance	16q22	AR	Myopathic mtDNA depletion	[xlii]
	TFAM	600438	mitochondrial transcription factor A	10q21.1	AR	Encephalomyopathy mtDNA depletion	[xliii]
	FBXL4	605654	mtDNA maintenance	6q16.1-q16.2	AR	Encephalomyopathy and myopathy mtDNA depletion	[xliv]
	MGME1	615084	mtDNA maintenance	20p11.23	AR	CPEO and Myopathy mtDNA depletion	[xlv]
Mitochondrial Import	DDP	304700	Protein import	Xq22	X-linked	Deafness-dystonia or Mohr-Tranebjaerg syndrome	[xlvi]
	DNAJC19	608977	Protein import	3q26.3	AR	Cardiomyopathy, ataxia	[xlvii]
Mitochondrial Protein Synthesis	AARS2	612035	Alanyl-tRNA synthetase	6p21.1	AR	Cardiomyopathy; Leukoencephalopathy	[xlviii]
	CARS2	612800	Cysteinyl-tRNA synthetase	13q34	AR	Myoclonic epilepsy	[xlix]
	DARS2	611105	aspartyl-tRNA synthetase	1q25.1	AR	Leukoencephalopathy and lactic acidosis	[l]
	EARS2	612799	Glutamyl tRNA synthetase	16p12.2	AR	Leukoencephalopathy	[li]
	FARS2	611592	Phenylalanyl-tRNA synthetase	6p25.1	AR	Alpers syndrome, spastic paraplegia	[lii]
	GARS	600287	glycyl-tRNA synthetase	7p14.3	AD	Charcot-Marie-Tooth disease	[liii]
	HARS2	600783	Histidyl-tRNA synthetase	5q31.3	AR	Perrault syndrome	[liv]
	IARS2	612801	Isoleucyl tRNA-Synthetase	1q41	AR	Cataract, deafness, neuropathy / Leigh Syndrome	[lv]
	KARS	601421	Lysyl-tRNA synthetase	16q23.1	AR	CMT disease/ Deafness	[lvi]
	LARS	615438	Leucine-tRNA synthetase	5q32	AR	Hepatopathy	[lvii]
	LARS2	604544	Leucyl-tRNA Synthetase	3p21.31	AR	Perrault Syndrome	[lviii]
	NARS2	612803	Asparaginyl-tRNA synthetase	11q14.1	AR	Alpers syndrome / Nonsyndromic Deafness and Leigh Syndrome	[lix]
	PARS2	612036	Prolyl- tRNA Synthetase	1p32.3	AR	Alpers syndrome	[lx]
	RARS2	611523	arginyl-tRNA synthetase	6q16.1	AR	Pontocerebellar hypoplasia	[lxi]
	SARS2	612804	seryl-tRNA synthetase	19q13.2	AR	Hyperuricemia, pulmonary hypertension, renal failure	[lxii]
	TARS2	612805	Threonyl--tRNA synthetase	1q21.2	AR	Encephalomyopathy	[lxiii]
	VARS2	612802	valyl-tRNA synthetase	6p21.33	AR	Encephalomyopathy	[lxiv]
	YARS2	610957	tyrosyl-tRNA synthetase	12p11.21	AR	Myopathy, lactic acidosis, and sideroblastic anemia-2	[lxv]
	EFG1	609060	Elongation factor G1 mitochondrial translation defect	3q25	AR	Severe hepatoencephalopathy and lactic acidosis	[lxvi]
	TSFM	604723	Mitochondrial translation elongation	12q13-q14	AR	Encephalomyopathy, hypertrophic cardiomyopathy	[lxvii]
	TUFM	602389	Mitochondrial translation elongation	16p11.2	AR	Leukodystrophy with micropolygyria	[lxviii]
	GTPBP3	608536	GTP-binding protein	19p13.11	AR	Cardiomyopathy, encephalopathy	[lxix]
	MTFMT	611766	Mitochondrial translation	15q22.31	AR	LS	[lxx]
	MTO1	614667	tRNA modification	6q13	AR	Cardiomyopathy	[lxxi]
	TRMT5	611023	mitochondrial tRNA methylation	14q23.1	AR	Cardiomyopathy/exercise intolerance	[lxxii]
	TRMT10C	615423	TRNA Methyltransferase	3q12.3	AR	Hypotonia, feeding difficulties, deafness	[lxxiii]
	TRMU	610230	mitochondrial translation	22q13.31	AR	Liver failure, deafness	[lxxiv]
	GFM1	606639	Mitochondrial translationelongation	3q25.32	AR	Encephalopathy/hepatic failure	[lxxv]
	GFM2	606544	Mitochondrial translation elongation	5q13.3	AR	Neurodevelopmental disorder, dysmorphic features	[lxxvi]
	C12orf65	613541	Mitochondrial translation	12q24.31	AR	Encephalomyopathy, Optic atrophy, axonal neuropathy, paraparesis	[lxxvii]
	RMND1	614917	Mitochondrial translation	6q25.1	AR	Encephalopathy	[lxxviii]
	MRPL3	607118	Mitochondrial translation	3q22.1	AR	Cardiomyopathy, mental retardation	[lxxix]
	MRPS7	611974	Mitochondrial translation	17q25.1	AR	Deafness, hepatic and renal failure	[lxxx]
	MRPL12	602375	Mitochondrial translation	17q25.3	AR	Growth retardation, encephalopathy	[lxxxi]
	MRPS16	609204	Mitochondrial translation	10q22.1	AR	Neonatal lactic acidosis corpus callosum agenesis	[lxxxii]
	MRPS22	605810	Mitochondrial translation	3q23	AR	Cardiomyopathy, tubulopathy	[lxxxiii]
	MRPL44	611849	Mitochondrial translation	2q36.1	AR	Cardiomyopathy	[lxxxiv]
Iron Homeostasis	FRDA (FXN)	606829	Frataxin Trinuc.* Repeat,	9q13	AR	Friedreich ataxia, neuropathy, cardiomyopathy, diabetes	[lxxxv]
	ABCB7	301310	Iron transport	Xq13.1-q13.3	X-linked	X-linked sideroblastic anemia with ataxia	[lxxxvi]
	GLRX5	205950	Iron-sulfur cluster biosynthesis	3p22.1	AR	Sideroblastic anemia	[lxxxvii]
	ISCU	255125	Iron-sulfur cluster biosynthesis	12q23.3	AR	Myopathy, lactic acidosis, exercise intolerance	[lxxxviii]
	BOLA3	613183	Iron-sulfur cluster biosynthesis	2p13.1	AR	Encephalomyopathy, cardiomyopathy	[lxxxix]
	NFU1	608100	Iron-sulfur cluster biosynthesis	2p13.3	AR	Lactic acidosis multiple respiratory chain deficiency	[xc]
	ISCA2	615317	Iron-sulfur cluster biosynthesis	14q24.3	AR	Leukodystrophy	[xci]
	IBA57	615316	Iron-sulfur cluster biosynthesis	1q42.13	AR	Myopathy, encephalopathy	[xcii]
	LYRM4	613311	Iron-sulfur cluster biosynthesis	6p25.1	AR	Lactic acidosis, Failure to thrive	[xciii]
	LYRM7	615831	Iron-sulfur cluster biosynthesis	5q23.3-q31.1	AR	Encephalopathy, lactic acidosis	[xciv]
	FDXL1	614585	Iron-sulfur cluster biosynthesis	19p13.2	AR	Myopathy, lactic acidosis	[xcv]
Coenzyme Q10 biogenesis	COQ2	609825	CoQ10 deficiency	4q21-q22	AR	Encephalomyopathy, nephropathy	[xcvi]
	COQ4	612898	CoQ10 deficiency	9q34.13	AR	Encephalomyopathy, mental retardation	[xcvii]
	COQ5	616359	CoQ10 deficiency	12q24.31	AR	Encephalomyopathy, cerebellar ataxia	[xcviii]
	COQ6	614647	CoQ10 deficiency	14q24.3	AR	Nephrotic syndrome, deafness	[xcix]
	COQ7	601683	CoQ10 deficiency	16p12.3	AR	Hypotonia, cardiac hypertrophy	[c]
	COQ9	612837	CoQ10 deficiency	16q13	AR	Neonatal lactic acidosis Seizures, cardiomyopathy	[ci]
	APTX	606350	CoQ10 deficiency	9p13.3	AR	Cerebellar ataxia Oculomotor apraxia	[cii]
	PDSS1	607429	CoQ10 deficiency	10p12.1	AR	Deafness, valvulopathy, mental retardation	[ciii]
	PDSS2	610564	CoQ10 deficiency	6q21	AR	LS, nephrotic syndrome	[civ]
	CABC1	606980	CoQ10 deficiency	1q42.2	AR	Cerebellar ataxia, lactic acidosis	[cv]
Chaperone Function	SPG7	607259	Paraplegin ATPase protease	16q24.3	AR	Spastic paraplegia	[cvi]
	HSPD1	118190	Mitochondrial chaperone	2q33.1	AR	Spastic paraplegia, leukodystrophy	[cvii]
Mitochondrial Integrity	DLP1	603850	Mitochondrial and peroxisomal fission	12p11.21	AD	Microcephaly, abnormal brain development, optic atrophy, lactic acidosis	[cviii]
	G4.5 (Tafazzin)	302060	Cardiolipin defect	Xq28	X-linked	Barth syndrome, X-linked dilated cardiomyopathy	[cix]
	RMRP	250250	RNAse Mitochondrial RNA Processing	9p13-p12	AR	Metaphyseal chondrodysplasia or Cartilage-hair hypoplasia	[cx]
Mitochondrial Metabolism	PDHA1	308930	Pyruvate dehydrogenase E1-a subunit	Xp22.2-p22.1	X-linked	LS	[cxi]
	ETHE1	602473	Ethylmalonic acid metabolism	19q13	AR	Encephalopathy, ethylmalonic aciduria	[cxii]
	PUS1	600462	pseudouridine synthase	12q24.33	AR	myopathy, lactic acidosis, and sideroblastic anemia	[cxiii]
	ATAD3	617183	mitochondrial dynamics	1p36.33	AR/AD	Neurodevelopmental disorder, pontocerebellar hypoplasia, encephalopathy	[cxiv]

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ABBREVIATIONS

AD: Autosomal Dominant; AR: Autosomal Recessive; 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: MyoNeuroGastroIntestinal Encephalopathy; MDDS: Mitochondrial DNA Depletion Syndrome

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REFERENCES

[i] 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. http://www.ncbi.nlm.nih.gov/pubmed/17557076

[ii] Ogilvie, I., Kennaway, N.G., Shoubridge, E.A., 2005. A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy. The Journal of Clinical Investigation 115, 2784-2792. http://www.ncbi.nlm.nih.gov/pubmed/16200211

[iii] 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., 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, 718-727. http://www.ncbi.nlm.nih.gov/pubmed/19463981

[iv] 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. http://www.ncbi.nlm.nih.gov/pubmed/18179882

[v] 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., Smeets, H.J., 2010. Defective complex I assembly due to C20orf7 mutations as a new cause of Leigh syndrome. Journal of Medical Genetics 47, 507-512. http://www.ncbi.nlm.nih.gov/pubmed/19542079
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., Thorburn, D.R., 2008. Mutation of C20orf7 disrupts complex I assembly and causes lethal neonatal mitochondrial disease. American Journal of Human Genetics 83, 468-478. http://www.ncbi.nlm.nih.gov/pubmed/18940309

[vi] Bianciardi, L., Imperatore, V., Fernandez-Vizarra, E., Lopomo, A., Falabella, M., Furini, S., Galluzzi, P., Grosso, S., Zeviani, M., Renieri, A., Mari, F., Frullanti, E., 2016. Exome sequencing coupled with mRNA analysis identifies NDUFAF6 as a Leigh gene. Molecular Genetics and Metabolism 119, 214-222. https://www.ncbi.nlm.nih.gov/pubmed/27623250

[vii] 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., Mootha, V.K., 2010. High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency. Nature Genetics 42, 851-858. http://www.ncbi.nlm.nih.gov/pubmed/20818383

[viii] Ibid.

[ix] 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., Prokisch, H., 2010. Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency. Nature Genetics 42, 1131-1134. http://www.ncbi.nlm.nih.gov/pubmed/21057504

[x] 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., Zeviani, M., 2009. SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy. Nature Genetics 41, 654-656. http://www.ncbi.nlm.nih.gov/pubmed/19465911

[xi] 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., Rutter, J., 2009. SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science 325, 1139-1142. http://www.ncbi.nlm.nih.gov/pubmed/19628817

[xii] 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. http://www.ncbi.nlm.nih.gov/pubmed/11528392
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. The New England Journal of Medicine 356, 809-819. http://www.ncbi.nlm.nih.gov/pubmed/17314340
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. http://www.ncbi.nlm.nih.gov/pubmed/12215968

[xiii] Tucker, E.J., Wanschers, B.F., Szklarczyk, R., Mountford, H.S., Wijeyeratne, X.W., van den Brand, M.A., Leenders, A.M., Rodenburg, R.J., Reljic, B., Compton, A.G., Frazier, A.E., Bruno, D.L., Christodoulou, J., Endo, H., Ryan, M.T., Nijtmans, L.G., Huynen, M.A., Thorburn, D.R., 2013. Mutations in the UQCC1-interacting protein, UQCC2, cause human complex III deficiency associated with perturbed cytochrome b protein expression. PLoS Genetics 9, e1004034. https://www.ncbi.nlm.nih.gov/pubmed/24385928

[xiv] Wanschers, B.F., Szklarczyk, R., van den Brand, M.A., Jonckheere, A., Suijskens, J., Smeets, R., Rodenburg, R.J., Stephan, K., Helland, I.B., Elkamil, A., Rootwelt, T., Ott, M., van den Heuvel, L., Nijtmans, L.G., Huynen, M.A., 2014. A mutation in the human CBP4 ortholog UQCC3 impairs complex III assembly, activity and cytochrome b stability. Human Molecular Genetics 23, 6356-6365. https://www.ncbi.nlm.nih.gov/pubmed/25008109

[xv] 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-1 in Leigh Disease associated with cytochrome c oxidase deficiency. American Journal of Human Genetics 63, 1609-1621. http://www.ncbi.nlm.nih.gov/pubmed/9837813
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. http://www.ncbi.nlm.nih.gov/pubmed/9843204

[xvi] Valnot, I., Osmond, S., Gigarel, N., Mehaye, B., Amiel, J., Cormier-Daire, V., Munnich, A., Bonnefont, J.P., Rustin, P., 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, 1104-1109. http://www.ncbi.nlm.nih.gov/pubmed/11013136

[xvii] 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 cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene. Nature Genetics 23, 333-337. http://www.ncbi.nlm.nih.gov/pubmed/10545952

[xviii] Antonicka, H., Leary, S.C., Guercin, G.H., Agar, J.N., Horvath, R., Kennaway, N.G., Harding, C.O., Jaksch, M., Shoubridge, E.A., 2003a. 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, 2693-2702. http://www.ncbi.nlm.nih.gov/pubmed/12928484
Valnot, I., Osmond, S., Gigarel, N., Mehaye, B., Amiel, J., Cormier-Daire, V., Munnich, A., Bonnefont, J.P., Rustin, P., 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, 1104-1109. http://www.ncbi.nlm.nih.gov/pubmed/11013136

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[lx] Ibid.

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[lxii] Belostotsky, R., Ben-Shalom, E., Rinat, C., Becker-Cohen, R., Feinstein, S., Zeligson, S., Segel, R., Elpeleg, O., Nassar, S., 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, 193-200. http://www.ncbi.nlm.nih.gov/pubmed/21255763

[lxiii] Diodato, D., Melchionda, L., Haack, T.B., Dallabona, C., Baruffini, E., Donnini, C., Granata, T., Ragona, F., Balestri, P., Margollicci, M., Lamantea, E., Nasca, A., Powell, C.A., Minczuk, M., Strom, T.M., Meitinger, T., Prokisch, H., Lamperti, C., Zeviani, M., Ghezzi, D., 2014. VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies. Human Mutation 35, 983-989. https://www.ncbi.nlm.nih.gov/pubmed/24827421

[lxiv] Ibid.

[lxv] 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., 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, 52-59. http://www.ncbi.nlm.nih.gov/pubmed/20598274

[lxvi] 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. The New England Journal of Medicine 351, 2080-2086. http://www.ncbi.nlm.nih.gov/pubmed/15537906

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[xc] Ibid.

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