Two different forms of inherited human TCRα chain deficiency
Bibliographic record
Abstract
Genetic defects that result in the absence of all T cells, including both αβ and γδ T cells, are classified as severe combined immunodeficiency (SCID), a life-threatening condition requiring immediate hematopoietic stem cell transplantation (HSCT) in affected newborns. Previously, patients with a homozygous c.*+1G>A splice variant in the T cell receptor (TCR) α constant chain (TRAC) were found to lack only αβ T cells and demonstrated longer survival compared with SCID patients lacking both αβ and γδ T cells. This observation suggested that γδ T cells might partially compensate for the absence of αβ T cells. Here, we describe two children with biallelic premature stop codons in TRAC. These mutations result in a complete loss of TCRαβ expression on the cell surface and an absence of αβ T cells, leading to severe immunodeficiency and early death. Additionally, we demonstrate that the previously reported c.*+1G>A TRAC variant retains partial activity in vitro, enabling low-level expression of functional TCRαβ. This residual expression likely explains the milder phenotype and extended survival observed in patients carrying this variant. In conclusion, we clarify the nonredundant role of αβ T cells in humans. Our findings show that complete TCRα deficiency causes a SCID-like clinical presentation, whereas partial TCRα deficiency is associated with milder clinical outcomes and longer survival.
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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 | 0.000 | 0.000 |
| 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 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".