P.079 MT-TA: A mitochondrial genome cause of developmental and epileptic encephalopathy
Bibliographic record
Abstract
Background: MT-TA (OMIM 590000), one of 22 mitochondrial transfer-RNA (mt-tRNA) genes, encodes the mt-tRNA for alanine. Pathogenic variants in mt-tRNA genes affect the translation of respiratory chain complexes I, III, and IV; which leads to mitochondrial dysfunction and a clinically variable phenotype. MT-TA pathogenic variants have been described in only seven patients, all of whom had isolated myopathy Methods: Case report. Results: Our patient initially presented with drug-resistant West syndrome, later evolving towards a Lennox Gastaut phenotype. Although she had hypotonia, serum creatine kinase and electromyography were normal. Brain-MRI showed bilateral symmetric hypointense T1, hyperintense T2-fluid-attenuated-inversion-recovery and restricted-diffusion signal changes in the dentate nuclei. Mitochondrial genome testing identified a previously published pathogenic variant in MT-TA (m.5591G>A) with 14% blood heteroplasmy and 16% urine heteroplasmy. The variant was absent in serum sampled from the patient’s mother Conclusions: Our case extends the phenotypic spectrum of MT-TA variants to include developmental and epileptic encephalopathy, in the apparent absence of muscle disease. We hypothesize that our patient may have the greatest degree of heteroplasmy in brain tissue; however, animal models and induced pluripotent stem cell (iPSC) models are needed to identify the precise mechanism by which MT-TA dysfunction results in variable phenotypes with variable degrees of heteroplasmy.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.003 | 0.001 |
| Insufficient payload (model declined to judge) | 0.021 | 0.007 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".