A novel cystic fibrosis mutation “delS1255” in a male diagnosed at birth
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Bibliographic record
Abstract
Cystic fibrosis (CF) is an autosomal recessive disorder caused by pathogenic variants in the CFTR gene. Over 2000 CFTR variants have been identified, and ongoing genetic characterization remains critical for guiding eligibility for CFTR modulator therapies and contributing to variant databases that support diagnosis and research. We describe a 20-year-old Caucasian male who is a compound heterozygous for the common F508del mutation and a novel variant, p.Ser1255del (c.3763_3765delTCA; delS1255). He was diagnosed with CF in the neonatal period following meconium ileus, confirmed by elevated sweat chloride testing. His clinical course included pancreatic insufficiency, chronic Staphylococcus aureus colonization, and sinus disease with nasal polyps, but no evidence of CF-related diabetes or liver disease. Molecular diagnostic testing conducted at Stanford Clinical Laboratory using PCR and bidirectional Sanger sequencing confirmed the F508del mutation and identified the previously unreported delS1255 variant, an in-frame deletion of a serine residue at position 1255. This variant is absent from population databases and a missense mutation at the same codon has previously been associated with severe CF phenotypes, supporting its likely pathogenicity. The patient was initiated on elexacaftor-tezacaftor-ivacaftor (ETI) therapy in 2021, based on the presence of the F508del allele. Since starting ETI, he has experienced substantial clinical improvement, including improved spirometry, radiology, and a marked reduction in sweat chloride concentration. The response is presumed to be driven by the F508del variant, while the effect of delS1255 on modulator responsiveness remains unknown. This case adds to the growing spectrum of CFTR variants with clinical relevance. • Identifies a previously unreported CFTR variant, p.Ser1255del • Describes the clinical features of a patient with F508del and delS1255 • Highlights diagnostic confirmation by sweat testing and gene sequencing • Explores the patient’s clinical response to modulator therapy • Contributes to expanding the known spectrum of CFTR variants
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.009 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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 it