A homozygous <scp>I684T</scp> in <scp>GLE1</scp> as a novel cause of arthrogryposis and motor neuron loss
Bibliographic record
Abstract
Mutations in GLE1 , RNA export mediator ( GLE1 ) gene have previously been shown to cause motor neuron diseases such as lethal congenital contracture syndrome 1 ( LCCS1 ) and lethal arthrogryposis with anterior horn cell disease ( LAAHD ), including arthrogryposis, fetal akinesis and motor neuron loss as common clinical features. The homozygous Fin Major mutation p.T144_E145insPFQ has been described as one of the causes for LCCS1 whereas LAAHD is caused by a heterocompound Fin Major mutation together with p. R569H , p. V617M or p. I684T missense mutation. None of these heterocompound missense mutations have previously been reported as homozygous states. Here we present the clinical features of 2 siblings with a homozygous p. I684T mutation in GLE1 . The patients suffered from similar, but milder symptoms than in LCCS1 and LAAHD , surviving up to 6 months before they died due to a progressive disease course including respiratory failure. Arthrogryposis, lack of spontaneous movements, and epilepsy were notable in both cases and lack of anterior horn cells was identified in autopsy samples. Our studies on patient‐derived fibroblasts show that the homozygous p. I684T impairs the nuclear localization of GLE1 further confirming the pathogenic role of this mutation.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.008 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".