Alternative titles; symbols
HGNC Approved Gene Symbol: MT-TP
SNOMEDCT: 129565002; ICD10CM: G72.9, M60-M63, M62.9; ICD9CM: 359.9;
The mitochondrial tRNA for proline is encoded by nucleotides 15955-16023 of the L-strand.
In a 7-year-old girl with pure myopathy, Moraes et al. (1993) found a G-to-A transition at mtDNA position 15990 changing the anticodon normally found in proline tRNAs (UGG) to the one found in serine tRNAs (UGA). This was the first example of a pathogenic anticodon alteration described in a higher eukaryote. The mutant mtDNA was heteroplasmic (85% mutant) in muscle but was undetectable in white blood cells from the patient and her mother. Analysis of single muscle fibers indicated that mutant mtDNAs severely impaired mitochondrial protein synthesis and respiratory chain activity, but only when present at greater than 90%. The 'recessive' behavior of this mtDNA alteration was thought to explain the patient's relatively mild clinical phenotype.
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 in the gene encoding tRNA(Thr) (MTTT; 590090.0001) and the other a 15965T-C transition in the MTTP gene. Restriction enzyme digestion failed to demonstrate the 15965T-C mutation in 100 control subjects and 47 Alzheimer cases.
In a woman with MERRF (545000), Blakely et al. (2009) identified a heteroplasmic 15967G-A transition in the MTTP gene. Skeletal muscle had a 69% mutant load, and the mutation segregated with cytochrome c oxidase activity in single muscle fibers. The patient had long-standing myoclonic epilepsy as well as other features, including proximal myopathy, sensorineural deafness, cerebellar ataxia, and pigmentary retinopathy. The mutation was not observed in the patient's unaffected mother or sibs, suggesting a de novo event.
Blakely, E. L., Trip, S. A., Swalwell, H., He, L., Wren, D. R., Rich, P., Turnbull, D. M., Omer, S. E., Taylor, R. W. A new mitochondrial transfer RNA(pro) gene mutation associated with myoclonic epilepsy with ragged-red fibers and other neurological features. Arch. Neurol. 66: 399-402, 2009. [PubMed: 19273760] [Full Text: https://doi.org/10.1001/archneurol.2008.576]
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]
Moraes, C. T., Ciacci, F., Bonilla, E., Ionasescu, V., Schon, E. A., DiMauro, S. A mitochondrial tRNA anticodon swap associated with a muscle disease. Nature Genet. 4: 284-288, 1993. [PubMed: 7689388] [Full Text: https://doi.org/10.1038/ng0793-284]