Clinical and Cellular Manifestations of <i>OSTM1</i>-Related Infantile Osteopetrosis
Bibliographic record
Abstract
UNLABELLED: Infantile ARO is a genetic disorder characterized by osteoclast dysfunction that leads to osteopetrosis. We describe a novel mutation affecting the OSTM1 locus responsible for ARO. In addition to common clinical features of osteopetrosis, the patient developed a unique neuronal pathology that provided evidence for an essential role of OSTM1 in normal neuronal cell development. INTRODUCTION: Infantile autosomal recessive osteopetrosis (ARO) is a genetic disorder characterized by osteoclast dysfunction that leads to osteopetrosis. We describe a novel mutation affecting the OSTM1 locus responsible for ARO. In addition to common clinical features of osteopetrosis, the patient developed a unique neuronal pathology that provided evidence for an essential role of OSTM1 in normal neuronal cell development. MATERIALS AND METHODS: We report a new case of ARO caused by an homozygous mutation in OSTM1. In addition to osteopetrosis and bone marrow failure, this patient also had neurological impairment not related to bone entrapment. Retinal dystrophy with absent evoked visual potentials and sensorineural deafness were documented, as well as cerebral atrophy and bilateral atrial subependymal heterotopias. RESULTS: The patient developed generalized seizures and had a profound developmental delay. Nerve biopsy failed to show inclusion material suggestive of neuroaxonal dystrophy. Bone marrow transplantation was declined considering the severe neurological compromise. The patient died at 1 yr of age. Osteoclasts derived from peripheral blood were mature and multinucleated. Expression analysis showed that the amount of OSTM1 cDNA transcript was significantly lowered but not absent. CONCLUSIONS: These results support the role of OSTM1 in osteoclast function and activation. However, they also suggest that OSTM1 has a primary role in neural development not related to lysosomal dysfunction.
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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 | 0.002 | 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".