Alternative titles; symbols
HGNC Approved Gene Symbol: MT-TC
SNOMEDCT: 39925003; ICD10CM: E88.41;
The mitochondrial tRNA for cysteine is encoded by nucleotides 5761-5826.
Manfredi et al. (1996) identified a heteroplasmic 5814A-G transition in the MTTC gene (590020.0001) in a 5-year-old girl of Portuguese origin who presented with MELAS (540000)-like symptoms at age 3. The same group (Santorelli et al., 1997) identified the 5814A-G mutation in an Italian family with a maternally inherited encephalomyopathy including progressive external ophthalmoplegia, seizures, and neurophysiologic evidence of brainstem dysfunction.
McFarland et al. (2007) identified a homoplasmic 5816A-G transition in the MTTC gene (590020.0002) in 4 maternally-related members of a family with a mitochondrial disorder with variable features, but most commonly including severe dystonia.
In a 5-year-old girl of Portuguese origin who presented with MELAS (540000) symptoms at age 3, Manfredi et al. (1996) identified a heteroplasmic 5814A-G transition in the MTTC gene within the D-stem. The mutation load in muscle and blood was high, above 90%, although analysis of individual muscle fibers showed a mutation load of 74 to 95%. The mutation was not found in 50 controls. The patient had episodic vomiting, lactic acidosis, seizures, and hemiparesis. Brain MRI showed diffuse white matter abnormalities in the frontal lobes and basal ganglia. However, ragged-red fibers were not noted on muscle biopsies, leading Manfredi et al. (1996) to use the term 'MELAS-like" to describe the phenotype.
The same group (Santorelli et al., 1997) identified the 5814A-G mutation in an Italian family with a maternally inherited encephalomyopathy including progressive external ophthalmoplegia, seizures, and neurophysiologic evidence of brainstem dysfunction. The proband was a 33-year-old woman who had normal development until adolescence, when she complained of easy fatigability and developed limitations of eye movements. By age 27, she also had hearing impairment, unsteady gait, hyporeflexia, nystagmus, and lactic acidosis. Brain MRI showed hyperintensities in the corpus callosum, posterior wall of the third ventricle, and brainstem. She later developed myoclonic jerks and generalized tonic-clonic seizures. Muscle biopsy showed ragged-red fibers and echocardiography showed abnormal repolarization and mild hypertrophy of the interventricular septum. She became ventilator-dependent and bedridden, and died at age 33. The mutation load was 96% in blood and 98% in muscle. Three maternal relatives also carried the mutation: the mother had moderate bradykinesia (mutation load of 88%), asymptomatic brother (74%), and teenage daughter (92%). All 3 relatives had abnormal neurophysiologic activity in the brainstem.
In 4 maternally-related members of a family with a mitochondrial disorder with variable features, but most commonly including severe dystonia, McFarland et al. (2007) identified a homoplasmic 5816A-G transition in the MTTC gene. Northern blot analysis showed about 30% residual levels of MTTC in patient muscle samples. Two brothers in the younger generation had onset in the late teens of seizures, tremor, and progressive dystonia affecting the limbs. One also had ptosis, optic atrophy, and jerky ocular pursuit movements. Two sibs in the older generation had onset in their forties of progressive dystonia; 1 also had seizures and the other had bulbar dysfunction, and ptosis. Muscle biopsies were normal, except in 1 of the younger patients, who had a mosaic pattern of COX deficiency, suggesting an mtDNA mutation. McFarland et al. (2007) emphasized the unusual presentation of a mitochondrial disease in this family.
Manfredi, G., Schon, E. A., Bonilla, E., Moraes, C. T., Shanske, S., DiMauro, S. Identification of a mutation in the mitochondrial tRNA-cys gene associated with mitochondrial encephalopathy. Hum. Mutat. 7: 158-163, 1996. [PubMed: 8829635] [Full Text: https://doi.org/10.1002/(SICI)1098-1004(1996)7:2<158::AID-HUMU12>3.0.CO;2-1]
McFarland, R., Chinnery, P. F., Blakely, E. L., Schaefer, A. M., Morris, A. A. M., Foster, S. M., Tuppen, H. A. L., Ramesh, V., Dorman, P. J., Turnbull, D. M., Taylor, R. W. Homoplasmy, heteroplasmy, and mitochondrial dystonia. Neurology 69: 911-916, 2007. [PubMed: 17724295] [Full Text: https://doi.org/10.1212/01.wnl.0000267843.10977.4a]
Santorelli, F. M., Siciliano, G., Casali, C., Basirico, M. G., Carrozzo, R., Calvosa, F., Sartucci, F., Bonfiglio, L., Murri, L., DiMauro, S. Mitochondrial tRNA(cys) gene mutation (A5814G): a second family with mitochondrial encephalopathy. Neuromusc. Disord. 7: 156-159, 1997. [PubMed: 9185178] [Full Text: https://doi.org/10.1016/s0960-8966(97)00444-6]