Mucolipidosis II: a single causal mutation in the <i>N</i>‐acetylglucosamine‐1‐phosphotransferase gene (<i>GNPTAB</i>) in a French Canadian founder population
Why this work is in the frame
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Bibliographic record
Abstract
Mucolipidosis (ML) II (I-cell disease) is a lysosomal storage disorder caused by a deficiency of UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase. MLII is an autosomal recessive disease with a carrier rate estimated at 1/39 in Saguenay-Lac-Saint-Jean (SLSJ) (Quebec, Canada), which is the highest frequency documented worldwide. To identify the causing mutation, we sequenced GNPTAB exons in 27 parents of 16 MLII-deceased children from the SLSJ region as obligatory and potential carriers. We also performed a genealogical reconstruction for each parent to evaluate consanguinity levels and genetic contribution of ancestors. Our goal was to identify which parameters could explain the high MLII frequency observed in the SLSJ population. A single mutation (c.3503_3504delTC) was found in all obligatory carriers. In addition, 11 apparent polymorphisms were identified. The mutation was not detected in genomic DNA of 50 unrelated controls. Genealogical data show six founders (three couples) with a higher probability of having introduced the mutation in the population. The frequency of the mutation was increased as a consequence of this founder effect and of the resulting population structure. We suggest that c.3503_3504delTC is the allele causing MLII in the SLSJ population, and its high carrier rate is most likely explained by a founder effect.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| 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 it