Identification of novel compound heterozygous mutation in Niemann-Pick disease type C gene (P14-11.006)
Bibliographic record
Abstract
Objective: To report a novel compound heterozygous mutation in two siblings with Niemann-Pick disease type C who displayed distinct phenotypic presentation Background: Niemann–Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disease with heterogenous neurological and systemic manifestations. The vast majority of cases (95%) are caused by mutations in the Niemann–Pick C1 protein (NPC1), whereas the reminder of cases are attributed to mutations in Niemann–Pick C2 protein (NPC2). Design/Methods: Case report Results: Case 1: A 57-year-old female presented with a 5-year history of progressive slowness, poor coordination, and cognitive decline. This was followed by generalized stiffness and recurrent ballistic movements within two years of onset. Her poor postural stability lead to frequent falls. Initial neurological evaluation revealed severe dysarthric speech, moderate vertical eye movement limitation, spasticity and exaggerated deep tendon reflexes, along with dystonic movements. She progressed rapidly, developing generalized dystonia which made her bedbound. Case 2: the young sibling of case 1, presented at the age of 56 with 8-year history of poor balance. Symptoms were slowly progressive, noted initially with changes in his balance, slurred speech, and poor coordination. He was also noticed to have mild cognitive changes. Examination revealed cerebellar dysarthria, with failure to generate saccades from primary position downwards. Deep tendon reflexes were brisk, with no evidence of muscle wasting, or spasticity. He showed signs of mild axial and appendicular ataxia. The progression was slow, and he maintained his mobility without requiring walking aids. Molecular genetic testing revealed compound heterozygous mutation in the NPC1 gene; c.180G>T (p.Gln60His) and c.3173C>A (p.Ala1058Asp). All biochemical results were within normal range. Brain MRI showed generalized cerebral and cerebellar volume loss few years into the onset of symptoms in both patients. Conclusions: Our report highlights the high intrafamilial heterogeneity and poor genotype-phenotype correlation in the case of Niemann–Pick disease type C. Disclosure: Dr. Abusrair has nothing to disclose. Dr. Amorelli has nothing to disclose. Justyna Sarna has nothing to disclose.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".