Alternative titles; symbols
HGNC Approved Gene Symbol: MT-TY
The mitochondrial tRNA for tyrosine is encoded by nucleotides 5826-5891.
In a patient with exercise intolerance, mild bilateral ptosis, limb weakness, and respiratory chain complex III deficiency, Pulkes et al. (2000) identified a novel heteroplasmic 5874A-G mutation in the mitochondrial tRNA tyrosine gene. Previous mutations associated with this clinical phenotype (excluding the ptosis) have been found in the mitochondrial cytochrome b gene (516020). The authors found that the tyrosine content is highest in the cytochrome b and COX III subunits, which may explain the clinical phenotype resulting from a defect in the tRNA-tyr gene. The mutation was found only in the patient's muscle and not in her blood or that of her relatives, suggesting somatic mutation.
In a female patient with chronic progressive external ophthalmoplegia, mild myopathy, and exercise intolerance, Raffelsberger et al. (2001) identified a single basepair deletion at position 5885 (5885delT) in the mitochondrial tRNA tyrosine gene. The deletion was found only in the patient's skeletal muscle tissue and not in her blood, in the blood of her relatives, or in more than 300 controls, suggesting somatic mutation. The deletion occurs in the aminoacyl-acceptor stem of the tRNA, a position that may produce a nonfunctional tRNA by affecting formation of secondary and tertiary protein structure.
Sahashi et al. (2001) reported a G-to-A transition at nucleotide 5877 of the MTTY gene in a 45-year-old woman with ptosis, external ophthalmoplegia, and proximal muscle weakness with onset at age 28 years. Her mother also had ptosis and carried the same mutation. Two children who carried the same mutation, ages 21 years and 19 years, were asymptomatic at the time of the study. Two asymptomatic paternal half sisters of the proband, ages 60 and 59 years, did not carry the mutation. Functional analysis of this mutation demonstrated that even at 23% of mutant mtDNA, oxygen consumption and cell viability were decreased. This mutation alters a residue essential in the formation of the L-shaped tertiary structure of tRNA.
Scaglia et al. (2003) identified a 5843A-G transition in the MTTY gene in a girl with onset of steroid-resistant nephrotic syndrome caused by focal segmental glomerulosclerosis at age 2 years, and onset of dilated cardiomyopathy at age 7 years. The mutation occurred in a highly conserved region of the gene and was determined to be homoplasmic in the patient's skeletal muscle, blood, and renal tissue. Skeletal muscle biopsy showed a combined respiratory chain defect and a partial deficiency of coenzyme Q10. The patient's mother, who had a history of migraine headaches, was also homoplasmic for the 5843A-G mutation. Scaglia et al. (2003) concluded that other epigenetic factors must be involved to explain the clinical variability between the patient and her mother.
Pulkes, T., Siddiqui, A., Morgan-Hughes, J. A., Hanna, M. G. A novel mutation in the mitochondrial tRNA-tyr gene associated with exercise intolerance. Neurology 55: 1210-1212, 2000. [PubMed: 11071502] [Full Text: https://doi.org/10.1212/wnl.55.8.1210]
Raffelsberger, T., Rossmanith, W., Thaller-Antlanger, H., Bittner, R. E. CPEO associated with a single nucleotide deletion in the mitochondrial tRNA-tyr gene. Neurology 57: 2298-2301, 2001. [PubMed: 11756614] [Full Text: https://doi.org/10.1212/wnl.57.12.2298]
Sahashi, K., Yoneda, M., Ohno, K., Tanaka, M., Ibi, T., Sahashi, K. Functional characterisation of mitochondrial tRNA(Tyr) mutation (5877G-A) associated with familial chronic progressive external ophthalmoplegia. (Letter) J. Med. Genet. 38: 703-705, 2001. [PubMed: 11594340] [Full Text: https://doi.org/10.1136/jmg.38.10.703]
Scaglia, F., Vogel, H., Hawkins, E. P., Vladutiu, G. D., Liu, L.-L., Wong, L.-J. C. Novel homoplasmic mutation in the mitochondrial tRNA-tyr gene associated with atypical mitochondrial cytopathy presenting with focal segmental glomerulosclerosis. Am. J. Med. Genet. 123A: 172-178, 2003. [PubMed: 14598342] [Full Text: https://doi.org/10.1002/ajmg.a.20315]