Familial Isolated Hyperparathyroidism Is Rarely Caused by Germline Mutation in<i>HRPT2</i>, the Gene for the Hyperparathyroidism-Jaw Tumor Syndrome
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Bibliographic record
Abstract
Familial isolated hyperparathyroidism (FIHP) can result occasionally from the incomplete expression of a syndromic form of familial hyperparathyroidism (HPT), specifically multiple endocrine neoplasia type 1 (MEN1), familial hypocalciuric hypercalcemia, or the hyperparathyroidism-jaw tumor syndrome (HPT-JT). The cause of FIHP has not been identified in the majority of families. We investigated 32 families with FIHP to determine the frequency of occult mutation in HRPT2, the gene causing HPT-JT. All families had negative clinical testing for MEN1, hypocalciuric hypercalcemia, and HPT-JT and negative mutational screening of MEN1 and CASR, the gene for the calcium-sensing receptor. Thus, an extended effort was made to exclude each of the principal syndromic causes of FIHP. The families were characterized by young probands (42 +/- 3 yr) and occasionally unusual parathyroid histology, including four families with one case of parathyroid cancer. We had speculated that there was a high frequency of occult mutation in HRPT2 among such carefully screened kindreds. This hypothesis became testable with the recent identification of that gene. Among the 32 FIHP families, only a single one was found to have a mutation in HRPT2 (679insAG); this mutation predicts premature truncation of its gene product, parafibromin, and thus its presumed inactivation. Even accounting for families with one of the three occult syndromes and false negative biochemical or DNA testing, these results indicate that an unexpectedly large fraction of FIHP has currently unrecognized causes.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 it