P.070 Autosomal dominant MARS mutation linked to severe early onset CMT2U
Bibliographic record
Abstract
Background: Methionyl-tRNA synthetase (MARS) links methionine to its cognate tRNA required for translation. MARS mutations have been linked to adult-onset CMT2U. Methods: The proband had weakness in her first year of life, sitting at 11 months and walking at 20 months old. At 4 years old she was areflexic with distal > proximal weakness. Nerve conduction studies showed normal median and sural sensory responses with absent common peroneal, low median and tibial motor amplitudes. EMG noted denervation and quadriceps biopsy revealed neurogenic atrophy. Genetic testing for spinal muscular atrophy and sequencing of MNF2, RAB7A, LMNA, MPZ, HSPB1, NEFL, GADP1, TRPV4, HSPB8, GJB1 and PLEK8G5 were negative. She stopped walking at 9 years old and could not raise her arms above her head at 11 years old. Results: Exome sequencing identified MARS: c.1189G>A; p.Ala397Thr. To determine the functional consequences of p.A397T-MARS, yeast complementation assays were performed. Wild type or mutant MARS were cloned into yeast lacking the endogenous MARS ortholog. Wild-type MARS supported robust cellular growth, while the p.A397T-MARS insert did not support cellular growth confirming deleterious effect of this variant. Conclusions: Our patient’s phenotype was similar to children with motor-predominant GARS mutations. Functional data notes this MARS variant to be damaging and predictive of a severe, early-onset phenotype.
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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) | 0.003 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.005 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
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".