Mitochondrial MTTL1 gene
The mitochondrial gene MT-TL1 encodes a transport RNA (tRNA) for leucine, triplet UUR (R for A or G). The gene is encoded by nucleotides 3230-3304. Diseases caused by mutations include Kearns-Sayre, MELAS, and MERFF syndromes, myopathy, cardiomyopathy, encephalopathy, ophthalmoplegia, and sudden infant death syndrome. Somatic mutations are observed with myelodysplastic syndrome. The ensemble of all mitochondrial genes is tested if a mitochondrial disorder has to be diagnosed.
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References:
1. |
Uusimaa J et al. (2007) Prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children.
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2. |
Silvestri G et al. (1994) A new mtDNA mutation in the tRNA(Leu(UUR)) gene associated with maternally inherited cardiomyopathy.
|
3. |
Odawara M et al. (1995) Prevalence and clinical characterization of Japanese diabetes mellitus with an A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene.
|
4. |
Matthews PM et al. (1995) Intracellular heteroplasmy for disease-associated point mutations in mtDNA: implications for disease expression and evidence for mitotic segregation of heteroplasmic units of mtDNA.
|
5. |
Yang CY et al. (1995) MELAS syndrome associated with diabetes mellitus and hyperthyroidism: a case report from Taiwan.
|
6. |
Manouvrier S et al. (1995) Point mutation of the mitochondrial tRNA(Leu) gene (A 3243 G) in maternally inherited hypertrophic cardiomyopathy, diabetes mellitus, renal failure, and sensorineural deafness.
|
7. |
Nakamura M et al. (2010) MERRF/MELAS overlap syndrome: a double pathogenic mutation in mitochondrial tRNA genes.
|
8. |
Yakubovskaya E et al. (2010) Helix unwinding and base flipping enable human MTERF1 to terminate mitochondrial transcription.
|
9. |
Li R et al. (2010) Human mitochondrial leucyl-tRNA synthetase corrects mitochondrial dysfunctions due to the tRNALeu(UUR) A3243G mutation, associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and diabetes.
|
10. |
Kaufmann P et al. (2009) Protean phenotypic features of the A3243G mitochondrial DNA mutation.
|
11. |
Sasarman F et al. (2008) The A3243G tRNALeu(UUR) MELAS mutation causes amino acid misincorporation and a combined respiratory chain assembly defect partially suppressed by overexpression of EFTu and EFG2.
|
12. |
Rajasimha HK et al. (2008) Selection against pathogenic mtDNA mutations in a stem cell population leads to the loss of the 3243A-->G mutation in blood.
|
13. |
de Vries D et al. (1994) Extreme variability of clinical symptoms among sibs in a MELAS family correlated with heteroplasmy for the mitochondrial A3243G mutation.
|
14. |
Janssen GM et al. (2007) The A3243G tRNALeu(UUR) mutation induces mitochondrial dysfunction and variable disease expression without dominant negative acting translational defects in complex IV subunits at UUR codons.
|
15. |
Durham SE et al. (2007) Normal levels of wild-type mitochondrial DNA maintain cytochrome c oxidase activity for two pathogenic mitochondrial DNA mutations but not for m.3243A-->G.
|
16. |
Jeppesen TD et al. (2006) Muscle phenotype and mutation load in 51 persons with the 3243A>G mitochondrial DNA mutation.
|
17. |
Donovan LE et al. (2006) Maternally inherited diabetes and deafness in a North American kindred: tips for making the diagnosis and review of unique management issues.
|
18. |
Pyle A et al. (2007) Depletion of mitochondrial DNA in leucocytes harbouring the 3243A->G mtDNA mutation.
|
19. |
Zeviani M et al. (1991) Maternally inherited myopathy and cardiomyopathy: association with mutation in mitochondrial DNA tRNA(Leu)(UUR).
|
20. |
Böhm M et al. (2006) Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency.
|
21. |
Stenqvist L et al. (2005) A juvenile case of MELAS with T3271C mitochondrial DNA mutation.
|
22. |
Jones M et al. (2004) MELAS A3243G mitochondrial DNA mutation and age related maculopathy.
|
23. |
Kirino Y et al. (2004) Codon-specific translational defect caused by a wobble modification deficiency in mutant tRNA from a human mitochondrial disease.
|
24. |
Chuang LM et al. (1995) Mitochondrial gene mutations in familial non-insulin-dependent diabetes mellitus in Taiwan.
|
25. |
None (1998) Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 39-1998. A 13-year-old girl with a relapsing-remitting neurologic disorder.
|
26. |
Chinnery PF et al. (1998) MELAS and MERRF. The relationship between maternal mutation load and the frequency of clinically affected offspring.
|
27. |
Majamaa K et al. (1998) Epidemiology of A3243G, the mutation for mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes: prevalence of the mutation in an adult population.
|
28. |
Wilichowski E et al. (1998) Pyruvate dehydrogenase complex deficiency and altered respiratory chain function in a patient with Kearns-Sayre/MELAS overlap syndrome and A3243G mtDNA mutation.
|
29. |
Hirai M et al. (1998) Mitochondrial deoxyribonucleic acid 3256C-T mutation in a Japanese family with noninsulin-dependent diabetes mellitus.
|
30. |
Zeviani M et al. (1998) Mitochondrial disorders.
|
31. |
Stone DL et al. (1997) Mitochondrial NP 3243 point mutation is not a common cause of VACTERL association.
|
32. |
Vilarinho L et al. (1997) The mitochondrial A3243G mutation presenting as severe cardiomyopathy.
|
33. |
Tamagawa Y et al. (1997) Audiologic findings in patients with a point mutation at nucleotide 3,243 of mitochondrial DNA.
|
34. |
Ogle RF et al. (1997) Mitochondrial myopathy with tRNA(Leu(UUR)) mutation and complex I deficiency responsive to riboflavin.
|
35. |
Reardon W et al. (1992) Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA.
|
36. |
Yorifuji T et al. (1996) Nephropathy and growth hormone deficiency in a patient with mitochondrial tRNA(Leu(UUR)) mutation.
|
37. |
Houshmand M et al. (1996) Fatal mitochondrial myopathy, lactic acidosis, and complex I deficiency associated with a heteroplasmic A --> G mutation at position 3251 in the mitochondrial tRNALeu(UUR) gne.
|
38. |
Feigenbaum A et al. (1996) The expanding clinical phenotype of the tRNA(Leu(UUR)) A-->G mutation at np 3243 of mitochondrial DNA: diabetic embryopathy associated with mitochondrial cytopathy.
|
39. |
Damian MS et al. (1996) VACTERL with the mitochondrial np 3243 point mutation.
|
40. |
Morten KJ et al. (1995) Multiple independent occurrence of the 3243 mutation in mitochondrial tRNA(leuUUR) in patients with the MELAS phenotype.
|
41. |
Hayashi J et al. (1993) Accumulation of mtDNA with a mutation at position 3271 in tRNA(Leu)(UUR) gene introduced from a MELAS patient to HeLa cells lacking mtDNA results in progressive inhibition of mitochondrial respiratory function.
|
42. |
Sweeney MG et al. (1993) Mitochondrial myopathy associated with sudden death in young adults and a novel mutation in the mitochondrial DNA leucine transfer RNA(UUR) gene.
|
43. |
Matthews PM et al. (1994) Comparison of the relative levels of the 3243 (A-->G) mtDNA mutation in heteroplasmic adult and fetal tissues.
|
44. |
Mariotti C et al. (1994) Defective respiratory capacity and mitochondrial protein synthesis in transformant cybrids harboring the tRNA(Leu(UUR)) mutation associated with maternally inherited myopathy and cardiomyopathy.
|
45. |
Morten KJ et al. (1993) A new point mutation associated with mitochondrial encephalomyopathy.
|
46. |
Moraes CT et al. (1992) The mitochondrial tRNA(Leu(UUR)) mutation in mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS): genetic, biochemical, and morphological correlations in skeletal muscle.
|
47. |
Sue CM et al. (1999) Infantile encephalopathy associated with the MELAS A3243G mutation.
|
48. |
Mosewich RK et al. (1993) The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes presenting without stroke.
|
49. |
Kobayashi Y et al. (1990) A point mutation in the mitochondrial tRNA(Leu)(UUR) gene in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes).
|
50. |
Goto Y et al. (1990) A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies.
|
51. |
Parsons T et al. (2010) Autonomic symptoms in carriers of the m.3243A>G mitochondrial DNA mutation.
|
52. |
Costello DJ et al. (2009) Efficacy of lamotrigine in disabling myoclonus in a patient with an mtDNA A3243G mutation.
|
53. |
Goto Y et al. (1991) A new mtDNA mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).
|
54. |
Janssen AJ et al. (2008) Muscle 3243A-->G mutation load and capacity of the mitochondrial energy-generating system.
|
55. |
Kobayashi Y et al. (1991) Respiration-deficient cells are caused by a single point mutation in the mitochondrial tRNA-Leu (UUR) gene in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS).
|
56. |
Enter C et al. (1991) A specific point mutation in the mitochondrial genome of Caucasians with MELAS.
|
57. |
Ciafaloni E et al. (1992) MELAS: clinical features, biochemistry, and molecular genetics.
|
58. |
Petruzzella V et al. (2004) Cerebellar ataxia as atypical manifestation of the 3243A>G MELAS mutation.
|
59. |
Latkany P et al. (1999) Mitochondrial maculopathy: geographic atrophy of the macula in the MELAS associated A to G 3243 mitochondrial DNA point mutation.
|
60. |
Moraes CT et al. (1993) Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot?
|
61. |
Lam CW et al. (1997) Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) triggered by valproate therapy.
|
62. |
Yoneda M et al. (1992) Marked replicative advantage of human mtDNA carrying a point mutation that causes the MELAS encephalomyopathy.
|
63. |
Elliott HR et al. (2008) Pathogenic mitochondrial DNA mutations are common in the general population.
|
64. |
Lertrit P et al. (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.
|
65. |
Opdal SH et al. (1999) Mitochondrial DNA point mutations detected in four cases of sudden infant death syndrome.
|
66. |
Velho G et al. (1996) Clinical phenotypes, insulin secretion, and insulin sensitivity in kindreds with maternally inherited diabetes and deafness due to mitochondrial tRNALeu(UUR) gene mutation.
|
67. |
Schulz JB et al. (1993) Mitochondrial gene mutations and diabetes mellitus.
|
68. |
van den Ouweland JM et al. (1992) Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness.
|
69. |
Deschauer M et al. (1999) Mitochondrial 3243 A-->G mutation (MELAS mutation) associated with painful muscle stiffness.
|
70. |
Goto Y et al. (1992) A novel point mutation in the mitochondrial tRNA(Leu)(UUR) gene in a family with mitochondrial myopathy.
|
71. |
Gattermann N et al. (2004) Ineffective hematopoiesis linked with a mitochondrial tRNA mutation (G3242A) in a patient with myelodysplastic syndrome.
|
72. |
Salpietro CD et al. (2003) A mitochondrial DNA mutation (A3243G mtDNA) in a family with cyclic vomiting.
|
73. |
Torroni A et al. (2003) Mitochondrial DNA haplogroups do not play a role in the variable phenotypic presentation of the A3243G mutation.
|
74. |
Olsson C et al. (2001) The level of the mitochondrial mutation A3243G decreases upon ageing in epithelial cells from individuals with diabetes and deafness.
|
75. |
Jaksch M et al. (2001) A mutation in mt tRNALeu(UUR) causing a neuropsychiatric syndrome with depression and cataract.
|
76. |
Deschauer M et al. (2001) Hearing impairment is common in various phenotypes of the mitochondrial DNA A3243G mutation.
|
77. |
Nagata H et al. (2001) Frequency and clinical features of patients with sensorineural hearing loss associated with the A3243G mutation of the mitochondrial DNA in otorhinolaryngic clinics.
|
78. |
Seneca S et al. (2001) A new mitochondrial point mutation in the transfer RNA(Leu) gene in a patient with a clinical phenotype resembling Kearns-Sayre syndrome.
|
79. |
Uimonen S et al. (2001) Hearing impairment in patients with 3243A-->G mtDNA mutation: phenotype and rate of progression.
|
80. |
Chinnery PF et al. (2001) No correlation between muscle A3243G mutation load and mitochondrial function in vivo.
|
81. |
De Kremer RD et al. (2001) Barth's syndrome-like disorder: a new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation).
|
82. |
Moilanen JS et al. (2001) Relative fitness of carriers of the mitochondrial DNA mutation 3243A > G.
|
83. |
Aggarwal P et al. (2001) Identification of mtDNA mutation in a pedigree with gestational diabetes, deafness, Wolff-Parkinson-White syndrome and placenta accreta.
|
84. |
Rahman S et al. (2001) Decrease of 3243 A-->G mtDNA mutation from blood in MELAS syndrome: a longitudinal study.
|
85. |
Chomyn A et al. (2000) The mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode syndrome-associated human mitochondrial tRNALeu(UUR) mutation causes aminoacylation deficiency and concomitant reduced association of mRNA with ribosomes.
|
86. |
Börner GV et al. (2000) Decreased aminoacylation of mutant tRNAs in MELAS but not in MERRF patients.
|
87. |
Yasukawa T et al. (2000) Modification defect at anticodon wobble nucleotide of mitochondrial tRNAs(Leu)(UUR) with pathogenic mutations of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.
|
88. |
Janssen GM et al. (1999) The diabetes-associated 3243 mutation in the mitochondrial tRNA(Leu(UUR)) gene causes severe mitochondrial dysfunction without a strong decrease in protein synthesis rate.
|
89. |
Bruno C et al. (1999) The mitochondrial DNA C3303T mutation can cause cardiomyopathy and/or skeletal myopathy.
|
90. |
Smith PR et al. (1999) Pigmentary retinal dystrophy and the syndrome of maternally inherited diabetes and deafness caused by the mitochondrial DNA 3243 tRNA(Leu) A to G mutation.
|
91. |
Orphanet article
Orphanet ID 138895
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92. |
NCBI article
NCBI 4567
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93. |
OMIM.ORG article
Omim 590050
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Update: Aug. 14, 2020