De Novo Mutations Causing Shwachman-Diamond Syndrome and a Founder Mutation in SBDS in the French Canadian Population
Bibliographic record
Abstract
We summarize the molecular findings in a patient cohort with Shwachman-Diamond syndrome that underwent genetic diagnostic testing. We could confirm a molecular diagnosis in 81 individuals. Our data is consistent with previous findings that the most common mutations in SBDS are recurrent gene conversion mutations in exon 2, c.258+2T>C or c.183_184delinsCT. The patients diagnosed either had two recurrent mutations (78%), or one recurrent mutation and a rare family-specific mutation (22%). We identified six unrelated individuals with SDS of French Canadian decent with the c.120del (p.Arg39fsX) mutation. Molecular analysis revealed that this mutation occurs with a founder haplotype. The opposing SBDS mutation present in these individuals was the common c.258+2T>C mutation, which was on a different haplotype in all five families. In addition, we estimated that approximately 9% (5 out of a subset of 54 patients with parent information) of the SDS individuals had a de novo mutation on one allele and an inherited mutation on the other allele. The de novo mutations were either recurrent gene conversion mutations (n=3) or rare point mutations (n=2). The occurrence of de novo mutation requires that parental carrier testing be performed for accurate familial risk assessment.
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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 | 0.000 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".