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| Mendeliome v1.3197 | MT-TH | Zornitza Stark Marked gene: MT-TH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3197 | MT-TH | Zornitza Stark Gene: mt-th has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3197 | MT-TH | Zornitza Stark Classified gene: MT-TH as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3197 | MT-TH | Zornitza Stark Gene: mt-th has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3196 | MT-TH |
Zornitza Stark gene: MT-TH was added gene: MT-TH was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-TH. Mode of inheritance for gene gene: MT-TH was set to MITOCHONDRIAL Publications for gene: MT-TH were set to 12682337; 14967777; 15111688; 21704194; 21931169; 23696415; 35092007; 24920829; 21704194 Phenotypes for gene: MT-TH were set to Mitochondrial disease (MONDO:0044970), MT-TH-related Review for gene: MT-TH was set to GREEN Added comment: DEFINITIVE by ClinGen. More than 5 individuals reported. Age of onset in affected individuals varied from adolescence to the 40s. Clinical features included stroke-like episodes, seizures, myoclonus, ataxia, optic atrophy, retinal dystrophy, cataracts, hearing loss, hypogonadism, and mood disorder. Cerebellar vermis hypoplasia and signal changes in the basal ganglia, dentate nuclei, temporal lobes, and occipital lobes were seen on brain imaging. Tissue biopsies identified ragged red fibers and COX-negative fibers. Laboratory investigations showed increased blood and cerebrospinal fluid lactate. Decreased activities of complexes I and IV were variably seen in muscle. Heteroplasmy levels of the variants in affected individuals ranged from 81% to homoplasmic in muscle, 33-87% in urine, 1-60% in blood, and undetectable to homoplasmic in fibroblasts. Single fiber testing, cybrid analysis, and Northern blot analysis further supported variant pathogenicity. This gene-disease relationship is also supported by known biochemical function and functional alteration in patient and non-patient cells (in vitro functional assays demonstrated reduced rates of mitochondrial translation as a result of variants in MT-TH; PMID: 24920829, 21704194). Sources: Expert list |
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