A G339R mutation in the <i>CTNS</i> gene is a common cause of nephropathic cystinosis in the south western Ontario Amish Mennonite population
Bibliographic record
Abstract
EDITOR-Guanylate cyclase (retGC-1) is a key enzyme in the recovery phase of phototransduction in both cone and rod photoreceptor cells. 1 Upon excitation by a photon of light, an enzymatic cascade of events occurs which leads to the hydrolysis of cGMP and the closure of the cGMP gated cation channels.This results in hyperpolarisation of the plasma membrane and the generation of a signal higher up in the visual pathway.Upon closure of the ion channels, the cytosolic levels of Ca 2+ decrease because export by the Na + , K + , Ca 2+ exchanger continues.This reduced Ca 2+ concentration results in the activation of retGC by activating proteins (GCAPs) and the increased conversion of GTP to cGMP, thus restoring the level of cGMP in the photoreceptors to their dark level.Mutations in GUCY2D, the gene encoding retGC-1, are a cause of Leber congenital amaurosis (LCA1), a recessive condition which manifests itself either at birth or during the first few months of life as total or near total blindness.2 3 Recently, we identified mutations in GUCY2D in four British families with autosomal dominant cone-rod dystrophy (AD-CORD).4 Subsequent to this, mutations in this gene were shown to be responsible for ADCORD in a French, 5 a Swiss, 6 and a Norwegian 7 family.In all seven families, the mutations are either in the same or in adjacent codons in a highly conserved region of the protein.In our four families and in the Swiss and Norwegian families, mutations were found in either codon 837 or 838, 4 6 7 whereas codons 837-839 each encode for an amino acid substitution in the French family.5 In order to determine whether ADCORD arising from mutations in GUCY2D are restricted to these codons and how important these mutations are to autosomal retinal disease in general, we have screened an additional group of unrelated patients diagnosed with autosomal dominant macular dystrophy or autosomal dominant cone or cone-rod dystrophy.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".