Variable expressivity in a family with an aggrecanopathy
Bibliographic record
Abstract
BACKGROUND: Osteochondritis dissecans is a condition wherein there is a subchondral bone lesion that causes pain, inflammation, and cartilage damage. Dominant Familial Osteochondritis Dissecans is a rare and severe form of osteochondritis dissecans (OCD). It is caused by heterozygous pathogenic variants in the gene encoding Aggrecan; ACAN. Aggrecan, a proteoglycan, is an essential component of the articular and growth plate cartilage. METHODS: Herein, we report three individuals from one family; the proband who presented with short stature, a lower limb bone exostosis, and bilateral knee and elbow OCD at the age of 13 years old. His twin brother presented with isolated short stature and his father with short stature and lumbar disc herniation. RESULTS: Next-generation sequencing of the ACAN gene in the proband identified a frameshift variant which is also present in the brother and father with short stature. The proband was treated surgically with bilateral elbow microfracture, after the failure of conservative therapy. CONCLUSION: To the best of our knowledge, this is the first patient with an aggrecanopathy who presents with osteochondritis dissecans due to a frameshift variant. This family presents with variable expressivity which might be attributed to modifier genes.
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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) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".