Autosomal dominant transmission of signal transduction and activator of transcription 1 (STAT1) mutation (Thr385Met) and extended lifespan
Bibliographic record
Abstract
Introduction: Heterozygous mutations in signal transducer and activator of transcription 1 (STAT1) have been associated with selective deficiencies to mycobacterial or fungal infections. Recent reports revealed that patients found to carry de novo heterozygous mutations in STAT1 encoding specific amino acid substitutions can go on to develop progressive combined immunodeficiency, distinct from the limited susceptibilities to infection previously reported for heterozygous STAT1 mutations. Objectives: We present a case of a mother and her son with chronic mucocutaneous candidiasis and T-cell dysfunction, both of whom lived longer than projected life expectancy with a heterozygous STAT1 mutation. The son lived to the age of 20 years and the mother to the age of 32 years. Methods: The son's blood sequencing of STAT1 was performed on a pure T-cell lineage at The Hospital for Sick Children and the Canadian Center for Primary Immunodeficiency, Toronto, Ontario. Results: STAT1 analysis revealed a heterozygous DNA binding domain mutation at Thr385Met. The patient proceeded to develop fulminant progressive multifocal leukoencephalopathy that ultimately led to his death. The patient's mother, although never confirmed to have STAT1 mutation with formal blood sequencing, had multiple comorbidities including progressive lymphopenia, hypogammaglobulinemia, recurrent Pseudomonas pneumonias with associated bronchiectasis, end-stage kidney disease requiring hemodialysis, and ultimately death due to multiple end organ failure associated sepsis. Conclusion: This is the first autosomal dominant transmission of the STAT1 DNA binding domain Thr385Met mutation with an extended lifespan. Statement of Novelty: Previous patients found to have heterozygous mutations of STAT1 that were associated with progressive combined immunodeficiency, arose de novo in each case. Presumed autosomal dominant transmission of a heterozygous STAT1 DNA binding domain Thr385Met mutation has not been reported.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 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".