Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders
Moldiag Diseases Genes Support Contact

Mitochondrial MTTL1 gene

Mutations of the mitochondrial tRNA may lead to MELAS syndrome or mitochondrial diabetes with deafness.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

MELAS syndrome
EHHADH
ND1
ND5
ND6
TRNC
TRNH
TRNK
TRNQ
TRNS1
TRNS2
Mitochondrial diabetes
TRNE
TRNK
TRNL1
TRNS2

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.

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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.

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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.

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5.

Yang CY et al. (1995) MELAS syndrome associated with diabetes mellitus and hyperthyroidism: a case report from Taiwan.

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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.

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7.

Nakamura M et al. (2010) MERRF/MELAS overlap syndrome: a double pathogenic mutation in mitochondrial tRNA genes.

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8.

Yakubovskaya E et al. (2010) Helix unwinding and base flipping enable human MTERF1 to terminate mitochondrial transcription.

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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.

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10.

Kaufmann P et al. (2009) Protean phenotypic features of the A3243G mitochondrial DNA mutation.

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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.

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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.

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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.

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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.

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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.

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16.

Jeppesen TD et al. (2006) Muscle phenotype and mutation load in 51 persons with the 3243A>G mitochondrial DNA mutation.

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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.

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18.

Pyle A et al. (2007) Depletion of mitochondrial DNA in leucocytes harbouring the 3243A->G mtDNA mutation.

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19.

Zeviani M et al. (1991) Maternally inherited myopathy and cardiomyopathy: association with mutation in mitochondrial DNA tRNA(Leu)(UUR).

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20.

Böhm M et al. (2006) Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency.

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21.

Stenqvist L et al. (2005) A juvenile case of MELAS with T3271C mitochondrial DNA mutation.

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22.

Jones M et al. (2004) MELAS A3243G mitochondrial DNA mutation and age related maculopathy.

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23.

Kirino Y et al. (2004) Codon-specific translational defect caused by a wobble modification deficiency in mutant tRNA from a human mitochondrial disease.

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24.

Chuang LM et al. (1995) Mitochondrial gene mutations in familial non-insulin-dependent diabetes mellitus in Taiwan.

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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.

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26.

Chinnery PF et al. (1998) MELAS and MERRF. The relationship between maternal mutation load and the frequency of clinically affected offspring.

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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.

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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.

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29.

Hirai M et al. (1998) Mitochondrial deoxyribonucleic acid 3256C-T mutation in a Japanese family with noninsulin-dependent diabetes mellitus.

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30.

Zeviani M et al. (1998) Mitochondrial disorders.

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31.

Stone DL et al. (1997) Mitochondrial NP 3243 point mutation is not a common cause of VACTERL association.

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32.

Vilarinho L et al. (1997) The mitochondrial A3243G mutation presenting as severe cardiomyopathy.

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33.

Tamagawa Y et al. (1997) Audiologic findings in patients with a point mutation at nucleotide 3,243 of mitochondrial DNA.

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34.

Ogle RF et al. (1997) Mitochondrial myopathy with tRNA(Leu(UUR)) mutation and complex I deficiency responsive to riboflavin.

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35.

Reardon W et al. (1992) Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA.

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36.

Yorifuji T et al. (1996) Nephropathy and growth hormone deficiency in a patient with mitochondrial tRNA(Leu(UUR)) mutation.

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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.

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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.

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39.

Damian MS et al. (1996) VACTERL with the mitochondrial np 3243 point mutation.

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40.

Morten KJ et al. (1995) Multiple independent occurrence of the 3243 mutation in mitochondrial tRNA(leuUUR) in patients with the MELAS phenotype.

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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.

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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.

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43.

Matthews PM et al. (1994) Comparison of the relative levels of the 3243 (A-->G) mtDNA mutation in heteroplasmic adult and fetal tissues.

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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.

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45.

Morten KJ et al. (1993) A new point mutation associated with mitochondrial encephalomyopathy.

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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.

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47.

Sue CM et al. (1999) Infantile encephalopathy associated with the MELAS A3243G mutation.

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48.

Mosewich RK et al. (1993) The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes presenting without stroke.

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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).

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50.

Goto Y et al. (1990) A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies.

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51.

Parsons T et al. (2010) Autonomic symptoms in carriers of the m.3243A>G mitochondrial DNA mutation.

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52.

Costello DJ et al. (2009) Efficacy of lamotrigine in disabling myoclonus in a patient with an mtDNA A3243G mutation.

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53.

Goto Y et al. (1991) A new mtDNA mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).

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54.

Janssen AJ et al. (2008) Muscle 3243A-->G mutation load and capacity of the mitochondrial energy-generating system.

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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).

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56.

Enter C et al. (1991) A specific point mutation in the mitochondrial genome of Caucasians with MELAS.

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57.

Ciafaloni E et al. (1992) MELAS: clinical features, biochemistry, and molecular genetics.

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58.

Petruzzella V et al. (2004) Cerebellar ataxia as atypical manifestation of the 3243A>G MELAS mutation.

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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.

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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?

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61.

Lam CW et al. (1997) Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) triggered by valproate therapy.

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62.

Yoneda M et al. (1992) Marked replicative advantage of human mtDNA carrying a point mutation that causes the MELAS encephalomyopathy.

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63.

Elliott HR et al. (2008) Pathogenic mitochondrial DNA mutations are common in the general population.

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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.

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65.

Opdal SH et al. (1999) Mitochondrial DNA point mutations detected in four cases of sudden infant death syndrome.

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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.

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67.

Schulz JB et al. (1993) Mitochondrial gene mutations and diabetes mellitus.

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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.

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69.

Deschauer M et al. (1999) Mitochondrial 3243 A-->G mutation (MELAS mutation) associated with painful muscle stiffness.

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70.

Goto Y et al. (1992) A novel point mutation in the mitochondrial tRNA(Leu)(UUR) gene in a family with mitochondrial myopathy.

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71.

Gattermann N et al. (2004) Ineffective hematopoiesis linked with a mitochondrial tRNA mutation (G3242A) in a patient with myelodysplastic syndrome.

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72.

Salpietro CD et al. (2003) A mitochondrial DNA mutation (A3243G mtDNA) in a family with cyclic vomiting.

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73.

Torroni A et al. (2003) Mitochondrial DNA haplogroups do not play a role in the variable phenotypic presentation of the A3243G mutation.

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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.

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75.

Jaksch M et al. (2001) A mutation in mt tRNALeu(UUR) causing a neuropsychiatric syndrome with depression and cataract.

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76.

Deschauer M et al. (2001) Hearing impairment is common in various phenotypes of the mitochondrial DNA A3243G mutation.

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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.

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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.

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79.

Uimonen S et al. (2001) Hearing impairment in patients with 3243A-->G mtDNA mutation: phenotype and rate of progression.

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80.

Chinnery PF et al. (2001) No correlation between muscle A3243G mutation load and mitochondrial function in vivo.

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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).

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82.

Moilanen JS et al. (2001) Relative fitness of carriers of the mitochondrial DNA mutation 3243A > G.

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83.

Aggarwal P et al. (2001) Identification of mtDNA mutation in a pedigree with gestational diabetes, deafness, Wolff-Parkinson-White syndrome and placenta accreta.

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84.

Rahman S et al. (2001) Decrease of 3243 A-->G mtDNA mutation from blood in MELAS syndrome: a longitudinal study.

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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.

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86.

Börner GV et al. (2000) Decreased aminoacylation of mutant tRNAs in MELAS but not in MERRF patients.

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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.

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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.

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89.

Bruno C et al. (1999) The mitochondrial DNA C3303T mutation can cause cardiomyopathy and/or skeletal myopathy.

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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.

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91.

Orphanet article

Orphanet ID 138895 external link
92.

NCBI article

NCBI 4567 external link
93.

OMIM.ORG article

Omim 590050 external link
Update: Aug. 14, 2020
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