An Intronic Polymorphism of the <i>hMLH1</i> Gene Contributes Toward Incomplete Genetic Testing for HNPCC
Bibliographic record
Abstract
Hereditary non-polyposis colorectal cancer (HNPCC) is a common hereditary cancer. Genetic testing is complicated by the multiple DNA mismatch repair genes that underlie the disorder. Many suspected HNPCC families have no germ-line mutation identified. We reassessed an unusual family that appeared to have 2 individuals homozygous for a germline mutation within exon 1 of the hMLH1 gene. A few rare individuals with two inherited mutations in one of the mismatch repair genes have been reported and appear to have a distinct clinical appearance. However, there were no clinical features in the family discussed here that were consistent with constitutive lack of hMLH1. Redesigning the intronic primers for exon 1 identified a common polymorphism located within the original intronic primer site. The polymorphism prevented amplification of the wild-type allele, giving the erroneous appearance of homozygous inheritance of the mutated allele. Likewise, common intronic polymorphisms, if located within primer sequences on the chromosome harboring the HNPCC germ-line mutation could restrict amplification to only the wild-type allele, which may contribute significantly to the low success rate of identifying mutations in HNPCC families.
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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 | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".