Alternative titles; symbols
HGNC Approved Gene Symbol: MT-TT
The mitochondrial tRNA for threonine is encoded by nucleotides 15888-15953.
Grasbon-Frodl et al. (1999) performed a complete sequence analysis of all 22 mitochondrially encoded tRNA genes in 20 cases of histologically proven idiopathic Parkinson disease (556500). Genomic DNA extracted from the substantia nigra of frozen or formalin-fixed and paraffin-embedded brains was used for amplification by PCR followed by automated sequencing. Two new homoplasmic point mutations were detected, one of which was a G-to-A transition at position 15950 of the MTTT gene. Restriction enzyme digestion failed to reveal the 15950G-A mutation in 96 controls and in 40 cases of neuropathologically confirmed Alzheimer disease.
This variant is classified as a variant of unknown significance because its contribution to lethal infantile mitochondrial myopathy (LIMM; 551000) has not been confirmed.
Yoon et al. (1991) described 2 patients with severe respiratory chain enzyme deficiency and associated lactic acidosis who died within days after birth. They detected an A-to-G mutation at nucleotide pair (np) 15924 in one patient and an A-to-G mutation at nucleotide pair 15923 in the other. Both mutations occurred within the tRNA anticodon stem-loop structure. Brown et al. (1992) screened 3 LIMM and multiple control subjects for these mutations and reported that the nucleotide pair 15924 A-to-G mutation found in one of the patients was not the primary cause of LIMM because the mutation was detected in the proband's unaffected mother. Furthermore, Brown et al. (1992) found the nucleotide pair 15924 mutation in approximately 11% (11/103) of Caucasian controls. The nucleotide pair 15923 mutation was not detected in 91 Caucasians, 35 Africans, and 57 Asians.
This variant is classified as a variant of unknown significance because its contribution to coronary heart disease has not been confirmed.
Jia et al. (2013) reported the clinical, genetic, molecular, and biochemical characterization of a 4-generation Han Chinese family with maternally inherited coronary heart disease. Thirteen of 32 adult members of this family exhibited variable severity and age of onset of coronary heart disease. Mutational analysis of their mitochondrial genomes identified the MTTT mutation 15927G-A belonging to the Eastern Asian haplogroup B5. The anticipated destabilization of a highly conserved basepairing by the 15927G-A mutation affects the structure and function of tRNA-thr. Northern analysis revealed an approximately 80% decrease in steady-state levels of mRNA in 15927G-A mutant cell lines. The mutation changed the conformation of tRNA-Thr, as suggested by slower electrophoretic mobility of mutated tRNA with respect to the wildtype molecule. In addition, an approximately 39% reduction in aminoacylated efficiency of tRNA-thr was observed in mutant cells derived from the Chinese family. In vivo mitochondrial protein labeling analysis showed approximately 53% reduction in the rate of mitochondrial translation in mutant cells. The impaired mitochondrial protein synthesis led to defects in overall respiratory capacity and specific substrate-driven respiration in mutant cells. An increased production of reactive oxygen species was observed in the mutant cells carrying this mutation.
Brown, M. D., Torroni, A., Shoffner, J. M., Wallace, D. C. Mitochondrial tRNA-thr mutations and lethal infantile mitochondrial myopathy. (Letter) Am. J. Hum. Genet. 51: 446-447, 1992. [PubMed: 1379415]
Grasbon-Frodl, E. M., Kosel, S., Sprinzl, M., von Eitzen, U., Mehraein, P., Graeber, M. B. Two novel point mutations of mitochondrial tRNA genes in histologically confirmed Parkinson disease. Neurogenetics 2: 121-127, 1999. [PubMed: 10369889] [Full Text: https://doi.org/10.1007/s100480050063]
Jia, Z., Wang, X., Qin, Y., Xue, L., Jiang, P., Meng, Y., Shi, S., Wang, Y., Mo, J. Q., Guan, M.-X. Coronary heart disease is associated with a mutation in mitochondrial tRNA. Hum. Molec. Genet. 22: 4064-4073, 2013. [PubMed: 23736300] [Full Text: https://doi.org/10.1093/hmg/ddt256]
Yoon, K. L., Aprille, J. R., Ernst, S. G. Mitochondrial tRNA-thr mutation in fatal infantile respiratory enzyme deficiency. Biochem. Biophys. Res. Commun. 176: 1112-1115, 1991. [PubMed: 1645537] [Full Text: https://doi.org/10.1016/0006-291x(91)90399-r]