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MT-TK

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mitochondrially encoded tRNA lysine
Identifiers
SymbolMT-TK
Alt. symbolsMERRF, MTTK
NCBI gene4566
HGNC7489
RefSeqNC_001807
Other data
LocusChr. MT[1]

Mitochondrially encoded tRNA lysinealso known asMT-TKis atransfer RNAwhich in humans is encoded by themitochondrialMT-TKgene.[1]

Structure

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TheMT-TKgene is located on thep armof themitochondrial DNAat position 12 and it spans 70 base pairs.[2]The structure of atRNAmolecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafedclover.[3]

Function

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MT-TK is a small 70 nucleotideRNA(human mitochondrial map position 8295-8364) that transfers the amino acidlysineto a growingpolypeptidechain at theribosomesite ofproteinsynthesis duringtranslation.

Clinical significance

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Mutations inMT-TKcan result in multiple mitochondrial deficiencies and associated disorders.

Myoclonic epilepsy with ragged-red fibers (MERRF)

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Mutations in theMT-TKgene are associated with myoclonic epilepsy and ragged-red fiber disease (MERRF).[4][5]Myoclonic epilepsy with ragged-red fibers (MERRF) is a disorder that affects many parts of the body, particularly the muscles andnervous system.In most cases, the signs and symptoms of this disorder appear during childhood oradolescence.The features of MERRF vary widely among affected individuals, even among members of the same family. Common symptoms include,myoclonus,myopathy,spasticity,epilepsy,peripheral neuropathy,dementia,ataxia,atrophyand more.[6]A majority of mutations in theMT-TKgene found to cause the disease were single nucleotide substitutions, such as 8344A>G. The 8344A>G mutation has been found to disable the normal functions of themitochondria.[7]A family of mutations 8344A>G and 16182A>C in theMT-TKgene has been found with MERRF syndrome. Another family with the syndrome exhibited mutations of 3243A>G and 16428G>A.[8]

MERRF/MELAS overlap syndrome

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MELAS syndrome may also be accompanied by another mitochondrial disorder calledmyoclonic epilepsy with ragged-red fibers,also known asMERRF syndrome.[9]In addition to symptoms of MELAS syndrome, additional signs and symptoms may include muscle twitches (myoclonus), difficulty coordinating movement (ataxia), and abnormal muscle cells known asragged-red fibers.The combination of MERRF and MELAS is called the MERRF/MELAS overlap syndrome. It has not been determined how mutations alter the energy production function of themitochondriaand result in symptoms of such syndromes.[7]The single nucleotide substitution 8356T>C has been found to cause the syndrome.[10]

Maternally inherited diabetes and deafness (MIDD)

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A mutation in theMT-TKgene has been found in a small number of people with maternally inherited diabetes and deafness (MIDD). The disorder is characterized bydiabetescombined withhearing loss,particularly of high pitches. Additional symptoms includemuscle weakness(myopathy) and various problems with a patient's eyes, heart, or kidneys. Mutations in theMT-TKgene disables theinsulinrelease by themitochondria.Diabetes results when thebeta cellsdo not release enough insulin to regulate blood sugar effectively. Researchers have not determined how mutations lead to hearing loss or the other features of MIDD.[7]The single nucleotide substitution 8296A>G has been found to cause the syndrome.[11]

Leigh syndrome

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The 8344A>G mutation in theMT-TKgene may also result inLeigh syndrome,a progressive brain disorder.[4]Clinical manifestations, which includevomiting,seizures,delayed development,myopathy,and problems with movement, have an early onset ofinfancyor early childhood. Additional symptoms include heart problems, kidney problems, and breathing difficulties. The cause of the disease has not been identified.[7]

Cardiomyopathy

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The 8363G>A mutation in theMT-TKgene may also cause hypertrophiccardiomyopathy,a disorder characterized by the thickening of the heart, andhearing loss.Additional symptoms may includemyopathyandataxia.[7]A family with abundant 8363G>A mutations ofMT-TKin their muscle samples exhibited symptoms ofencephalomyopathy,sensorineural hearing loss,andhypertrophic cardiomyopathy.[12]

Complex IV Deficiency

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MT-TKmutations have been associated with complex IV deficiency of themitochondrial respiratory chain,also known as thecytochrome c oxidasedeficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, includingskeletal muscles,theheart,thebrain,or theliver.Common clinical manifestations includemyopathy,hypotonia,andencephalomyopathy,lactic acidosis,andhypertrophic cardiomyopathy.[13]A patient with a 8313G>A mutation in theMT-TKgene exhibited symptoms of the deficiency accompanied by bilateralptosis.[14]Other variants also include 8328G>A[15]and 8344G>A.[16]

References

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  1. ^Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG (April 1981). "Sequence and organization of the human mitochondrial genome".Nature.290(5806): 457–65.Bibcode:1981Natur.290..457A.doi:10.1038/290457a0.PMID7219534.S2CID4355527.
  2. ^ "MT-TK mitochondrially encoded tRNA lysine [Homo sapiens (human)] - Gene - NCBI".ncbi.nlm.nih.gov.
  3. ^"tRNA / transfer RNA".Learn Science at Scitable.
  4. ^abShoffner JM, Lott MT, Lezza AM, Seibel P, Ballinger SW, Wallace DC (June 1990). "Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation".Cell.61(6): 931–7.doi:10.1016/0092-8674(90)90059-N.PMID2112427.S2CID6101099.
  5. ^Yoneda M, Tanno Y, Horai S, Ozawa T, Miyatake T, Tsuji S (August 1990). "A common mitochondrial DNA mutation in the t-RNA(Lys) of patients with myoclonus epilepsy associated with ragged-red fibers".Biochemistry International.21(5): 789–96.PMID2124116.
  6. ^"Myoclonic epilepsy with ragged-red fibers".Genetics Home Reference.U.S. National Library of Medicine.Public DomainThis article incorporates text from this source, which is in thepublic domain.
  7. ^abcdeReference, Genetics Home."MT-TK gene".Genetics Home Reference.Public DomainThis article incorporates text from this source, which is in thepublic domain.
  8. ^Zsurka G, Hampel KG, Kudina T, Kornblum C, Kraytsberg Y, Elger CE, Khrapko K, Kunz WS (February 2007)."Inheritance of mitochondrial DNA recombinants in double-heteroplasmic families: potential implications for phylogenetic analysis".American Journal of Human Genetics.80(2): 298–305.doi:10.1086/511282.PMC1785346.PMID17236134.
  9. ^Melone MA, Tessa A, Petrini S, Lus G, Sampaolo S, di Fede G, Santorelli FM, Cotrufo R (February 2004). "Revelation of a new mitochondrial DNA mutation (G12147A) in a MELAS/MERFF phenotype".Archives of Neurology.61(2): 269–72.doi:10.1001/archneur.61.2.269.PMID14967777.S2CID9418186.
  10. ^Silvestri G, Moraes CT, Shanske S, Oh SJ, DiMauro S (December 1992)."A new mtDNA mutation in the tRNA(Lys) gene associated with myoclonic epilepsy and ragged-red fibers (MERRF)".American Journal of Human Genetics.51(6): 1213–7.PMC1682905.PMID1361099.
  11. ^Kameoka K, Isotani H, Tanaka K, Azukari K, Fujimura Y, Shiota Y, Sasaki E, Majima M, Furukawa K, Haginomori S, Kitaoka H, Ohsawa N (April 1998). "Novel mitochondrial DNA mutation in tRNA(Lys) (8296A-->G) associated with diabetes".Biochemical and Biophysical Research Communications.245(2): 523–7.doi:10.1006/bbrc.1998.8437.PMID9571188.
  12. ^Santorelli FM, Mak SC, El-Schahawi M, Casali C, Shanske S, Baram TZ, Madrid RE, DiMauro S (May 1996)."Maternally inherited cardiomyopathy and hearing loss associated with a novel mutation in the mitochondrial tRNA(Lys) gene (G8363A)".American Journal of Human Genetics.58(5): 933–9.PMC1914622.PMID8651277.
  13. ^Reference, Genetics Home."Cytochrome c oxidase deficiency".Genetics Home Reference.Public DomainThis article incorporates text from this source, which is in thepublic domain.
  14. ^O'Rourke K, Buddles MR, Farrell M, Howley R, Sukuraman S, Connolly S, Turnbull DM, Hutchinson M, Taylor RW (October 2009). "Phenotypic diversity associated with the mitochondrial m.8313G>A point mutation".Muscle & Nerve.40(4): 648–51.doi:10.1002/mus.21342.PMID19618438.S2CID5872401.
  15. ^Houshmand M, Lindberg C, Moslemi AR, Oldfors A, Holme E (1999)."A novel heteroplasmic point mutation in the mitochondrial tRNA(Lys) gene in a sporadic case of mitochondrial encephalomyopathy: de novo mutation and no transmission to the offspring".Human Mutation.13(3): 203–9.doi:10.1002/(SICI)1098-1004(1999)13:3<203::AID-HUMU4>3.0.CO;2-3.PMID10090475.S2CID29433711.
  16. ^Mancuso M, Petrozzi L, Filosto M, Nesti C, Rocchi A, Choub A, Pistolesi S, Massetani R, Fontanini G, Siciliano G (March 2007). "MERRF syndrome without ragged-red fibers: the need for molecular diagnosis".Biochemical and Biophysical Research Communications.354(4): 1058–60.doi:10.1016/j.bbrc.2007.01.099.PMID17275787.
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This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.

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