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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 lysine also known as MT-TK is a transfer RNA which in humans is encoded by the mitochondrial MT-TK gene.[1]

Structure

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The MT-TK gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 70 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3]

Function

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MT-TK is a small 70 nucleotide RNA (human mitochondrial map position 8295-8364) that transfers the amino acid lysine to a growing polypeptide chain at the ribosome site of protein synthesis during translation.

Clinical significance

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Mutations in MT-TK can result in multiple mitochondrial deficiencies and associated disorders.

Myoclonic epilepsy with ragged-red fibers (MERRF)

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Mutations in the MT-TK gene 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 and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. 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, atrophy and more.[6] A majority of mutations in the MT-TK gene 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 the mitochondria.[7] A family of mutations 8344A>G and 16182A>C in the MT-TK gene 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 called myoclonic epilepsy with ragged-red fibers, also known as MERRF 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 as ragged-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 the mitochondria and 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 the MT-TK gene has been found in a small number of people with maternally inherited diabetes and deafness (MIDD). The disorder is characterized by diabetes combined with hearing loss, particularly of high pitches. Additional symptoms includemuscle weakness (myopathy) and various problems with a patient's eyes, heart, or kidneys. Mutations in the MT-TK gene disables the insulin release by the mitochondria. Diabetes results when the beta cells do 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 the MT-TK gene may also result in Leigh syndrome, a progressive brain disorder.[4] Clinical manifestations, which include vomiting, seizures, delayed development, myopathy, and problems with movement, have an early onset of infancy or 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 the MT-TK gene may also cause hypertrophic cardiomyopathy, a disorder characterized by the thickening of the heart, and hearing loss. Additional symptoms may include myopathy and ataxia.[7] A family with abundant 8363G>A mutations of MT-TK in their muscle samples exhibited symptoms of encephalomyopathy, sensorineural hearing loss, and hypertrophic cardiomyopathy.[12]

Complex IV Deficiency

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MT-TK mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy.[13] A patient with a 8313G>A mutation in the MT-TK gene exhibited symptoms of the deficiency accompanied by bilateral ptosis.[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. PMID 7219534. S2CID 4355527.
  2. ^ "MT-TK mitochondrially encoded tRNA lysine [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov.
  3. ^ "tRNA / transfer RNA". Learn Science at Scitable.
  4. ^ a b Shoffner 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. PMID 2112427. S2CID 6101099.
  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. PMID 2124116.
  6. ^ "Myoclonic epilepsy with ragged-red fibers". Genetics Home Reference. U.S. National Library of Medicine.Public Domain This article incorporates text from this source, which is in the public domain.
  7. ^ a b c d e Reference, Genetics Home. "MT-TK gene". Genetics Home Reference.Public Domain This article incorporates text from this source, which is in the public 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. PMC 1785346. PMID 17236134.
  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. PMID 14967777. S2CID 9418186.
  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. PMC 1682905. PMID 1361099.
  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. PMID 9571188.
  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. PMC 1914622. PMID 8651277.
  13. ^ Reference, Genetics Home. "Cytochrome c oxidase deficiency". Genetics Home Reference.Public Domain This article incorporates text from this source, which is in the public 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. PMID 19618438. S2CID 5872401.
  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. PMID 10090475. S2CID 29433711.
  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. PMID 17275787.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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