Clinical Phenotypes (non-LHON) Associated with mtDNA rRNA & tRNA Mutations Reported in the Literature

Syndromes Locus Disease* Allele RNA Ho* He* Status** References
Encephalomyopathy, Leigh Syndrome MTTV LS C1624T tRNA Val + - Prov (85)
Encephalomyopathy, Leigh Syndrome MTTV Adult LS G1644T tRNA Val - + Prov (16)
Encephalomyopathy Leigh Syndrome MTTW MILS A5537insT tRNA Trp - + Prov (112)
 
Encephalomyopathy MERRF MTTK MERRF A8344G tRNA Lys - + Cfrm (6, 38, 71, 99, 116, 125, 126, 144, 166, 170)
Encephalomyopathy MERRF MTTK MERRF T8356C tRNA Lys - + Cfrm (83,129,174)
Encephalomyopathy MERRF MTTK MERRF G8361A tRNA Lys - + Prov (107)
Encephalomyopathy MERRF MTTK MERRF/MICM+DEAF/Autism G8363A tRNA Lys - + Prov (100,109)
Encephalomyopathy MERRF MTTL1 MERRF/KSS overlap G3255A tRNA Leu (UUR) - + Prov (97)
Encephalomyopathy MERRF MTTF MERRF G611A tRNA Phe - + Prov (76)
Encephalomyopathy Myoclonus and Psychomotor Regression MTTD MEPR A7543G tRNA Asp - + Prov (127)
Encephalomyopathy Ataxia, Myoclonus and Deafness MTTV AMDF G1606A tRNA Val - + Prov (153)
Encephalomyopathy MERRF MTTH MERRF-MELAS / Cerebral edema G12147A tRNA His - + Cfrm (86,147)
 
Encephalomyopathy MELAS MTTL1 MELAS A3243G tRNA Leu (UUR) - + Cfrm (19, 24, 31, 38, 47, 55, 61, 68, 69, 102)
Encephalomyopathy MELAS MTTL1 MELAS G3244A tRNA Leu (UUR) - + Prov (66)
Encephalomyopathy MELAS MTTL1 MELAS A3252G tRNA Leu (UUR) - + Prov (30,92)
Encephalomyopathy MELAS MTTL1 MELAS C3256T tRNA Leu (UUR) - + Cfrm (90,113)
Encephalomyopathy MELAS MTTL1 MELAS/Myopathy T3258C tRNA Leu (UUR) - + Prov (134)
Encephalomyopathy MELAS MTTL1 MELAS T3271C tRNA Leu (UUR) - + Conf (30, 32, 46, 70, 108, 140, 154)
Encephalomyopathy MELAS MTTL1 MELAS T3291C tRNA Leu (UUR) - + Prov (30,34)
Encephalomyopathy MELAS MTTV MELAS G1642A tRNA Val - + Prov (22)
Encephalomyopathy MELAS MTTQ MELAS/Encephalopathy G4332A tRNA Gln - + Cfrm (5)
Encephalomyopathy MELAS MTTF MELAS G583A tRNA Phe - + Prov (41)
Encephalomyopathy MELAS MTRNR2 MELAS C3093G 16S rRNA - + Prov (51)
 
Encephalomyopathy MTTL1 PEM T3271delT tRNA Leu (UUR) - + Prov (123)
Encephalomyopathy MTTI Progressive Encephalopathy T4290C tRNA Ile + + Prov (74)
Encephalomyopathy MTTI Mitochondrial Encephalocardiomyopathy C4320T tRNA Ile - + Prov (110)
Encephalomyopathy MTTW Encephalomyopathy G5540A tRNA Trp - + Prov (128)
Encephalomyopathy MTTC Encephalopathy T5814C tRNA Cys - + Prov (77,135)
Encephalomyopathy MTTS1 PEM/AMDF C7472insC tRNA Ser (UCN) + + Cfrm (58,59,115,152)
Encephalomyopathy MTTS1 PEM/MERME T7512C tRNA Ser (UCN) + + Prov (58,59,95)
Encephalomyopathy MTTK Encephalopathy C8302T tRNA Lys + - Unclear (134)
Encephalomyopathy MTTK Mitochondrial Encephalopathy G8328A tRNA Lys - + Prov (49)
Encephalomyopathy MTTG PEM T10010C tRNA Gly - + Prov (8)
Encephalomyopathy MTATT Encephalomyopathy G15915A tRNA Thr - + Prov (98,118)
 
Encephaolmyopathy Rett Syndrome MTRNR2 Rett Syndrome C2835T rRNA 16S - + Prov (14,142)
Multisystem Disease MTTI Varied familial presentation G4284A tRNA Ile - + Prov (20)
Encephalomyopathy Gastrointestinal Reflux and Sudden Infant Death Syndrome MTTG GER/SIDS A10044G tRNA Gly - + Prov (111)
 
Mitochondrial Myopathy MTTF MM T582C tRNA Phe - + Prov (93)
Mitochondrial Myopathy MTTF MM T618C tRNA Phe - + Prov (67)
Mitochondrial Myopathy MTTL1 MM G3242A tRNA Leu (UUR) + - Prov (66)
Mitochondrial Myopathy MTTL1 MM/CPEO A3243G TRNA Leu(UUR) - + Cfrm (60,91)
Mitochondrial Myopathy MTTL1 MM A3243T tRNA Leu(UUR) - + Prov (121)
Mitochondrial Myopathy MTTL1 MM/CPEO T3250C tRNA Leu (UUR) - + Prov (33,36)
Mitochondrial Myopathy MTTL1 MM A3251G tRNA Leu (UUR) - + Prov (139)
Mitochondrial Myopathy MTTL1 MM C3254G tRNA Leu (UUR) - + Prov (65)
Mitochondrial Myopathy MTTL1 Myopathy A3280G tRNA Leu (UUR) - + Prov (134)
Mitochondrial Myopathy MTTL1 Myopathy A3288G TRNA Leu(UUR) - + Prov (37)
Mitochondrial Myopathy MTTL1 MM A3302G tRNA Leu (UUR) - + Cfrm (9,50)
Mitochondrial Myopathy MTTI MM A4267G tRNA Ile - + Prov (148)
Mitochondrial Myopathy MTTQ Myopathy T4370AT tRNA Gln - + Prov (23)
Mitochondrial Myopathy MTTM MM T4409C tRNA Met - + Prov (165)
Mitochondrial Myopathy MTTM MM G4450A tRNA Met - + Prov (135)
Mitochondrial Myopathy MTTW MM G5521A tRNA Trp - + Prov (130)
Mitochondrial Myopathy MTTS1 MM T7480G tRNA Ser (UCN) - + Prov (7)
Mitochondrial Myopathy MTTS1 MM G7497A tRNA Ser (UCN) + + Prov (59)
Mitochondrial Myopathy MTTK Myopathy T8355C tRNA Lys - + Prov (134)
Mitochondrial Myopathy MTTK Myopathy T8362G tRNA Lys - + Prov (134)
Mitochondrial Myopathy MTTG Myopathy G10014A tRNA Gly + - Unclear (134)
Mitochondrial Myopathy MTTL2 MM A12320G tRNA Leu (CUN) - + Prov (167)
Mitochondrial Myopathy MTTE MM+DM T14709C tRNA Glu - + Conf (40,42,164)
Mitochondrial Myopathy MTTT MM T15940delT tRNA Thr + - Prov (119)
Mitochondrial Myopathy MTTP MM C15990T tRNA Pro - + Prov (56,89)
Mitochondrial Myopathy, Exercise Intolerance MTTY Exercise Intolerance T5874G tRNA Tyr - + Prov (105)
 
Mitochondrial Myopathy, CPEO MTTL1 CPEO C3254T tRNA Leu (UUR) + - Prov (66)
Mitochondrial Myopathy, CPEO MTTI CPEO T4274C tRNA Ile - + Prov (17)
Mitochondrial Myopathy, CPEO MTTI CPEO T4285C tRNA Ile - + Prov (132)
Mitochondrial Myopathy, CPEO MTTI CPEO/MS G4298A tRNA Ile - + Prov (146)
Mitochondrial Myopathy, CPEO MTTI CPEO G4309A tRNA Ile - + Prov (27)
Mitochondrial Myopathy, CPEO MTTA CPEO T5628C tRNA Ala - + Prov (133)
Mitochondrial Myopathy, CPEO MTTN CPEO/MM T5692C tRNA Asn - + Prov (94,117,134)
Mitochondrial Myopathy, CPEO MTTN CPEO/MM G5698A tRNA Asn - + Prov (134)
Mitochondrial Myopathy, CPEO MTTN CPEO/MM G5703G tRNA Asn - + Prov (43,90)
Mitochondrial Myopathy, CPEO MTTK CPEO + Myoclonus G8342A tRNA Lys - + Prov (151)
Mitochondrial Myopathy, CPEO MTTL2 CPEO G12294A tRNA Leu (CUN) - + Prov (104)
Mitochondrial Myopathy, CPEO MTTL2 CPEO/Stroke/CM A12308G tRNA Leu (CUN) nd nd P.M. (48, 71, 81, 88, 90, 99, 106, 160)
Mitochondrial Myopathy, CPEO MTTL2 CPEO T12311C tRNA Leu (CUN) + + Prov (44,113)
Mitochondrial Myopathy, CPEO MTTL2 CPEO G12315A tRNA Leu (CUN) - + Prov (28)
Mitochondrial Myopathy, Ocular Myopathy MTTL1 Ocular myopathy T3273C tRNA Leu (UUR) - + Prov (13)
Mitochondrial Myopathy, KSS MTTL1 KSS G3249A tRNA Leu (UUR) - + Prov (120)
 
Mitochondrial Myopathy Cytopathy MTTY Mitochondrial Cytopathy/ FSGS A5843G tRNA Tyr + - Prov (114)
Mitochondrial Myopathy Cytopathy MTTK Mitochondrial cytopathy A8326G tRNA Lys - + Prov (169)
Mitochondrial Myopathy Cytopathy MTTP Mitochondrial cytopathy G15995A tRNA Pro - + Prov (169)
Mitochondrial Myopathy with Myoglobinuria MTTF Myoglobinuria A606G TRNA Phe - + Prov (18)
 
Mitochondrial Myopathy, Gastrointestinal Syndrome MTTW Gastrointestinal Syndrome G5532A tRNA Trp - + Prov (78)
Mitochondrial Myopathy,  Mitochondrial Neurogastrointestinal Encephalomyopathy MTTK MNGIE G8313A tRNA Lys - + Prov (163)
Mitochondrial Myopathy with Chronic Intestinal Pseudoobstruction MTTG CIPO A10006G tRNA Gly nd nd Prov (71,94)
Mitochondrial Myopathy with Chronic Intestinal Pseudoobstruction MTTS1 CIPO C12246G tRNA Ser (AGY) nd nd Prov (71,94)
 
Mitochondrial Myopathy with Renal Dysfunction MTTF Tubulointerstitial nephritis A608G tRNA Phe + - Prov (158)
 
Mitochondrial Myopathy Lethal Infantile Mitochondrial Myopathy MTTT LIMM A15923G tRNA Thr nd - Prov (11,171,172)
Mitochondrial Myopathy Lethal Infantile Mitochondrial Myopathy MTTT LIMM A15924G tRNA Thr nd - P.M. (11,101,171)
 
Mitochondrial Myopathy and cardiomyopathy MTTL1 MMC A3260G tRNA Leu (UUR) - + Cfrm (80,138,173)
Mitochondrial Myopathy and cardiomyopathy MTTL1 MMC C3303T tRNA Leu (UUR) + + Prov (131)
Maternaly Inherited Hypertrophic Cardiomyopathy MTTI MHCM A4295G tRNA Ile - + Prov (87)
Maternally Inherited Cardiomyopathy MTTI MICM A4300G tRNA Ile - + Prov (15)
Cardiomyopathy MTTK Cardiomyopathy A8348G tRNA Lys - + Prov (149)
Maternally Inherited Hypertrophic Cardiomyopathy MTTG MHCM T9997C tRNA Gly nd + Prov (88)
Maternally Inherited Cardiomyopathy MTTH MICM G12192A tRNA His + - Prov (122)
Cardiomyopathy MTTL2 Dilated Cardiomyopathy T12297C tRNA Leu (CUN) - + Prov (35)
 
Fatal Infantile Cardiomyopathy Plus (MELAS) MTTI FICP A4269G tRNA Ile - + Prov (45,143)
Fatal Infantile Cardiomyopathy Plus (MELAS) MTTI FICP A4317G tRNA Ile nd nd Prov (57,141)
 
Deafness MTRNR1 DEAF A827G 12S rRNA + - Prov (73)
Deafness MTRNR1 DEAF T961C 12S rRNA + - Prov (73)
Deafness MTRNR1 DEAF T961delT+C(n)ins 12S rRNA + + Prov (4)
Deafness MTRNR1 DEAF T961insC 12S rRNA + - Prov (4)
Deafness MTRNR1 DEAF T1005C 12S rRNA + - Prov (73)
Deafness
Sensory Neural Hearing Loss
MTRNR1 SNHL T1095C 12S rRNA + + Cfrm (150)
Deafness MTRNR1 DEAF A1116G 12S rRNA + - Prov (73)
Deafness MTRNR1 DEAF C1494T 12S rRNA + - Prov (175)
Deafness MTRNR1 DEAF A1555G 12S rRNA + - Cfrm (26, 53, 84, 103, 155, 157, 159)
Deafness
Sensory Neural Hearing Loss
MTTS1 SNHL T7510C tRNA Ser (UCN) - + Prov (54)
Deafness
Sensory Neural Hearing Loss
MTTS1 SNHL T7511C tRNA Ser(UCN) + + Prov (136)
Deafness
cerebellar dysfunction
MTTS1 Deafness and Cerebellar Dysfunction 7472insC tRNA Ser(UCN) - + Prov (152)
Deafness MTTH DEAF + RP G12183A tRNA His - + Prov (21)
Deafness Ataxia and MR MTTE Deafness, Mental Retaration, Cerebellar Dysfunction 14709G tRNA Glu - + Prov (40)
 
Diabetes Mellitus MTRNR1 DM C1310T 12S + - Prov (145)
Diabetes Mellitus MTRNR1 DM A1438G 12S + - Prov (145)
Diabetes Mellitus & Deafness MTTL1 DM / DMDF A3243G tRNA Leu (UUR) - + Cfrm (1, 2, 12, 29, 39, 62, 79, 82, 161, 162)
Diabetes Mellitus MTTL1 DM T3264C tRNALeu (UUR) - + Prov (137)
Diabetes Mellitus MTTL1 DM T3271C tRNA Leu (UUR) - + Prov (156)
Diabetes Mellitus
Metabolic Syndrome
MTTI Metabolic Syndrome & Hypomagnesemia T4291C tRNA Ile + - Prov (168)
Diabetes Mellitus & Deafness & Cardiomyopathy MTTK DMDF/MERRF/HCM A8296G tRNA Lys - + Prov (3,63,64)
Diabetes Mellitus & Deafness MTTS2 DMDF C12258A tRNA Ser (AGY)   + Prov (75)
 
Movement Disorder MTTV Movement Disorder T1659C tRNA Val - + Prov (10)
Alzheimer & Parkinson Disease MTRNR2 ADPD G3196A rRNA 16S + + Prov (124)
Alzheimer & Parkinson Disease
Deafness & Migraine
MTTQ ADPD/Hearing loss and migraine T4336C tRNA Gln + _ Unclear (25,52,72,124)
Dementia and Chorea MTTW DEMCHO G5549A tRNA Trp - + Prov (96)
Abbreviations
* Plasmy: Ho, homoplasmy; He, heteroplasmy
* Disease: AD, Alzheimer's Disease; ADPD, Alzheimer's Disease and Parkinsons's Disease; CIPO Chronic Intestinal Pseudoobstruction with myopathy and Ophthalmoplegia; CPEO, Chronic Progressive External Ophthalmoplegia; DEMCHO, Dementia and Chorea; DM, Diabetes Mellitus; DMDF Diabetes Mellitus & DeaFness; EXIT, exercise intolerance; FBSN Familial Bilateral Striatal Necrosis; FICP Fatal Infantile Cardiomyopathy Plus, a MELAS-associated cardiomyopathy; HCM, Hypertrophic CardioMyopathy; LS, Leigh Syndrome; MELAS, Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes; MERRF Myoclonic Epilepsy and Ragged Red Muscle Fibers; MHCM Maternally Inherited Hypertrophic Cardiomyopathy; MICM Maternally Inherited Cardiomyopathy; MM, mitochondrial myopathy; NAION Nonarteritic Anterior Ischemic Optic Neuropathy; NARP, Neurogenic muscle weakness, Ataxia, and Retinitis Pigmentosa; NIDDM, Non-Insulin Dependent Diabetes Mellitus; SNHL, Sensorineural Hearing Loss.
* *Status: Cfrm, considered confirmed by multiple reports in the literature; Prov, provisional isolated report(s), not yet confirmed by multiple labs; P.M., reported originally in the literature at pathogenic but now generally considered to be a polymorphic variant.

References

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165. Vissing, J., Salamon, M. B., Arlien-Soborg, P., Norby, S., Manta, P., DiMauro, S. and Schmalbruch, H. (1998). "A new mitochondrial tRNA(Met) gene mutation in a patient with dystrophic muscle and exercise intolerance." Neurology 50(6):1875-1878.

166. Wallace, D. C., Zheng, X., Lott, M. T., Shoffner, J. M., Hodge, J. A., Kelley, R. I., Epstein, C. M. and Hopkins, L. C. (1988). "Familial mitochondrial encephalomyopathy (MERRF): Genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease." Cell 55(4):601-610.

167. Weber, K., Wilson, J. N., Taylor, L., Brierley, E., Johnson, M. A., Turnbull, D. M. and Bindoff, L. A. (1997). "A new mtDNA mutation showing accumulation with time and restriction to skeletal muscle." American Journal of Human Genetics 60(2):373-380.

168. Wilson, F. H., Hariri, A., Farhi, A., Zhao, H., Petersen, K. F., Toka, H. R., Nelson-Williams, C., Raja, K. M., Kashgarian, M., Shulman, G. I., Scheinman, S. J. and Lifton, R. P. (2004). "A cluster of metabolic defects caused by mutation in a mitochondrial tRNA." Science 306(5699):1190-1194.

169. Wong, L. J., Liang, M. H., Kwon, H., Bai, R. K., Alper, O. and Gropman, A. (2002). "A cystic fibrosis patient with two novel mutations in mitochondrial DNA: mild disease led to delayed diagnosis of both disorders." American Journal of Medical Genetics 113(1):59-64.

170. Yoneda, M., Tanno, Y., Horai, S., Ozawa, T., Miyatake, T. and Tsuji, S. (1990). "A common mitochondrial DNA mutation in the tRNALys of patients with myoclonus epilepsy associated with ragged-red fibers." Biochemistry International 21(5):789-796.

171. Yoon, K. L., Aprille, J. R. and Ernst, S. G. (1991). "Mitochondrial tRNAThr mutation in fatal infantile respiratory enzyme deficiency." Biochemical and Biophysical Research Communications 176(3):1112-1115.

172. Yoon, K. L., Ernst, S. G., Rasmussen, C., Dooling, E. C. and Aprille, J. R. (1993). "Mitochondrial disorder associated with newborn cardiopulmonary arrest." Pediatric Research 33(5):433-440.

173. Zeviani, M., Gellera, C., Antozzi, C., Rimoldi, M., Morandi, L., Villani, F., Tiranti, V. and DiDonato, S. (1991). "Maternally inherited myopathy and cardiomyopathy: association with mutation in mitochondrial DNA tRNALeu(UUR)." Lancet 338(8760):143-147.

174. Zeviani, M., Muntoni, F., Savarese, N., Serra, G., Tiranti, V., Carrara, F., Mariotti, C. and DiDonato, S. (1993). "A MERRF/MELAS overlap syndrome associated with a new point mutation in the mitochondrial DNA tRNALys gene." European Journal of Human Genetics 1(1):80-87.

175. Zhao, H., Li, R., Wang, Q., Yan, Q., Deng, J. H., Han, D., Bai, Y., Young, W. Y. and Guan, M. X. (2004). "Maternally inherited aminoglycoside-induced and nonsyndromic deafness is associated with the novel C1494T mutation in the mitochondrial 12S rRNA gene in a large Chinese family." American Journal of Human Genetics 74(1):139-152.

This table is reproduced with permission from PRINCIPLES AND PRACTICE OF MEDICAL GENETICS, 5/e. � 2006 Elsevier Ltd.
Topic revision: r2 - 13 Oct 2016, MarieLott
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