Targeted Sequencing of HEXA Gene Shows Missense Substitution (p.Arg499His) in a Large Pakistani Family with Tay-Sachs Disease
Bibliographic record
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 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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 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) | 0.000 | 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 teacher head, 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".