Dosage Effect of a Dominant CLCN1 Mutation: A Novel Syndrome
Bibliographic record
Abstract
Multiple mutations in the CLCN1 gene coding for the voltage-gated chloride channel have been documented to cause myotonia congenita. We report a kindred featuring an index patient who possesses 2 copies of a dominantly inherited mutated CLCN1 allele with a resulting novel phenotypic presentation. The index patient is a boy who presented initially for evaluation at the age of 5 years with a 2-year history of gait problems. Both parents and 3 male siblings were entirely well. Examination revealed a striking diffuse muscular hypertrophy, diffuse mild to moderate weakness, Gower sign, percussion, and grip myotonia. Electromyography confirmed myotonia, and molecular analysis revealed 2 copies of the T310M mutation on the CLCN1 gene. Testing of family members revealed a normal neurological examination without clinical myotonia in all and electromyographic evidence of myotonia and a single copy of the T310M mutation in both parents and 2 siblings. Our kindred is the initial demonstration of the dosage effect of a dominant mutated allele in the CLCN1 gene.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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 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".