A Rare Case of De novo C634G Germline Mutation of the RET Proto-Oncogene in a Patient With MEN 2A Syndrome With Aggressive Pheochromocytoma
Bibliographic record
Abstract
Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal inherited disorder induced by mutations in the RET proto-oncogene. It is characterized by medullary thyroid carcinoma (MTC), accompanied in half of cases by pheochromocytoma and less frequently, by primary hyperparathyroidism. The aim of the study was to investigate a clinical case of a MEN 2A syndrome consisting of bilateral aggressive pheochromocytomas and MTC with loco-regional lymph node invasion caused by a rare de novo germline mutation in the RET proto-oncogene (Cys634Gly). We reported herein a 42-year-old man presented with hypertension refractory to various antihypertensive drug regimens administered over the preceding 3 years. Abdominal computed tomography scan showed a large right adrenal mass, and a smaller left adrenal nodule. Comprehensive biochemical analyses ( 24-hour urinary catecholamines and metabolites ) confirmed the diagnosis of pheochromocytoma. 123 I-metaiodobenzylguanidine scintigraphy revealed uptake in the left inferior thyroid nodule. Left t hyroid ultrasound-guided f ine needle aspiration established the diagnosis of MTC. The patient first underwent open right adrenalectomy, and 2 months later, total thyroidectomy with central neck compartment lymph node dissection. Screening for hyperparathyroidism was negative. On follow-up, the patient demonstrated no biochemical abnormalities, or clinical complaints. Genetic testing identified a point mutation in the RET proto-oncogene , confirming the diagnosis of MEN 2A. This missense mutation, located in exon 11, resulted in the replacement of a cysteine 634 residue with glycine. To the best of our knowledge, this is the first MEN 2A case reported with de novo Cys634Gly RET germline mutation in North America, and also worldwide with regard to the aggressiveness of this genotypic variant. doi: http://dx.doi.org/10.4021/jem120w
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.002 | 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 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".