Which gene is mutated in MEN 1 syndrome?

Explanation

## MEN 1 Syndrome Genetics **Key Point:** MEN 1 is caused by mutations in the MENIN gene (chromosome 12q13), which encodes a tumor suppressor protein. ### Gene Function The MENIN protein acts as a tumor suppressor by: - Regulating histone methylation and gene transcription - Controlling cell proliferation and apoptosis - Suppressing multiple endocrine tumors ### Inheritance Pattern - Autosomal dominant inheritance - Penetrance >95% by age 40 - Loss of heterozygosity (two-hit hypothesis) leads to tumor formation **High-Yield:** MENIN mutations account for ~90% of familial MEN 1 cases and ~10% of sporadic primary hyperparathyroidism cases. ### Clinical Manifestations ("3 P's") 1. **Parathyroid** tumors (95% of patients) → hyperparathyroidism 2. **Pancreatic** neuroendocrine tumors (60–70%) → gastrinomas, insulinomas 3. **Pituitary** adenomas (20–40%) → prolactinomas most common **Clinical Pearl:** Screening for MEN 1 in young patients with primary hyperparathyroidism or multiple endocrine tumors is essential for early diagnosis and family counseling.