Targeted Sequencing of HEXA Gene Shows Missense Substitution (p.Arg499His) in a Large Pakistani Family with Tay-Sachs Disease
Bibliographic record
Abstract
Abstract Tay-Sachs disease or GM2 gangliosidosis, is caused by a deficiency of beta-hexosaminidase A (HEXA), resulting in lysosomal accumulation of GM2 ganglioside. However, deficiencies or reduced activities of HEXA and HEXB result in Sandhoff disease. The patients manifest with the macular cherry-red spots due to lipid-laden ganglion cells, hypotonia, low muscle tone, intractable seizures, developmental arrest, blindness, and neurological deterioration. The aim of this study was to identify the TSD-causing variant in a large Pakistani family showing typical symptoms of Tay-Sachs disease. Here, we studied a large Pakistani family with six TSD patients for the identification of the pathogenic variant by targeted DNA sequencing. As a result, we identified a missense substitution (p.Arg499His) in exon 13 of HEXA that was completely cosegregated among affected and normal individuals. In conclusion, we identified a missense substitution (p.Arg499His) in HEXA gene in a large consanguineous Pakistani family and further enriched the mutational spectrum of HEXA through Pakistani patients for the early diagnosis of the disease.
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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 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".