A novel nonsense mutation in WNK1/HSN2 associated with sensory neuropathy and limb destruction in four siblings of a large Iranian pedigree
Bibliographic record
Abstract
BACKGROUND: Hereditary sensory and autonomic neuropathy type 2 (HSAN2) is an autosomal recessive disorder with predominant sensory dysfunction and severe complications such as limb destruction. There are different subtypes of HSAN2, including HSAN2A, which is caused by mutations in WNK1/HSN2 gene. METHODS: An Iranian family with four siblings and autosomal recessive inheritance pattern whom initially diagnosed with HSAN2 underwent whole exome sequencing (WES) followed by segregation analysis. RESULTS: According to the filtering criteria of the WES data, a novel candidate variation, c.3718C > A in WNK1/HSN2 gene that causes p.Tyr1025* was identified. This variation results in a truncated protein with 1025 amino acids instead of the wild-type product with 2645 amino acids. Sanger sequencing revealed that the mutation segregates with disease status in the pedigree. CONCLUSIONS: The identified novel nonsense mutation in WNK1/HSN2 in an Iranian HSAN2 pedigree presents allelic heterogeneity of this gene in different populations. The result of current study expands the spectrum of mutations of the HSN2 gene as the genetic background of HSAN2A as well as further supports the hypothesis that HSN2 is a causative gene for HSAN2A. However, it seems that more research is required to determine the exact effects of this product in the nervous system.
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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 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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) | 0.000 | 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".