Identification of a mutation in the Indian Hedgehog (<i>IHH</i>) gene causing brachydactyly type A1 and evidence for a third locus
Bibliographic record
Abstract
Brachydactyly (BD) is a term used to describe inherited anomalies of the hands generally characterised by shortened phalanges or metacarpals. Initially, the brachydactylies were grouped into five different classes (A-E), with three subtypes of A.1 Later work revised and extended the classification of BD.2,3 In type A, shortening is primarily confined to the middle phalanges. Subtype A1 (BDA1, OMIM 112500) is distinguished by hypoplastic middle phalanges (especially the 2nd and 5th digits), with either distal or terminal symphalangism depending on the severity. In addition, shortening of the proximal phalanges of the thumb, the metacarpals, metatarsals, or the big toe are also observed in these patients. Short stature is often associated with BDA1 patients. Despite being the first syndrome described with Mendelian autosomal dominant inheritance in 1903,4, the genetic aetiology of BDA was not reported until 2001.5 Suspecting that cell proliferation or differentiation factors could be the culprit causing BDA1, our group screened markers near several candidate genes in two families diagnosed with BDA1. No linkage was observed.6 We also chose to look for mutations of the PAX3 genes in these families by direct sequencing of all the exons, but no significant mutation was identified (unpublished data). In 2000, a locus for BDA1 was mapped to 2q35-q36 in two unrelated Chinese families.7 Refined mapping and mutation screening of candidate genes in the region by the same group identified missense mutations in the Indian Hedgehog gene ( IHH) of the affected subjects in three unrelated families.5 The missense mutations, located at the amino terminus of the IHH protein, are conserved among the Hedgehog family proteins. Local and long range cell proliferation signalling functions were suggested to reside within the amino-terminus domain. Interestingly, ROR2 and CDMP1 have been identified to cause brachydactyly types B and …
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".