A 35-year-old woman with neurofibromatosis type 2 (NF2) develops bilateral sensorineural hearing loss and tinnitus. MRI shows bilateral acoustic schwannomas. Which gene mutation underlies this condition?
- A NF2 (merlin/schwannomin) — tumor suppressor on chromosome 22 linking cytoskeleton to cell membrane ✓
- B NF1 (neurofibromin) — tumor suppressor on chromosome 17 regulating RAS-GTP
- C VHL (von Hippel-Lindau) — tumor suppressor involved in HIF-1α regulation
- D PTEN — tumor suppressor regulating PI3K-AKT-mTOR pathway
Explanation
Neurofibromatosis type 2 (NF2) is caused by germline mutations in the NF2 gene on chromosome 22q12, encoding merlin (schwannomin), a cytoskeletal linker protein related to the ERM (ezrin-radixin-moesin) family that regulates cell proliferation and contact inhibition. The hallmark is bilateral vestibular schwannomas (acoustic neuromas), often presenting in the 2nd–3rd decade with bilateral hearing loss, tinnitus, and balance disturbance. NF1 mutations cause café-au-lait spots, peripheral neurofibromas, and Lisch nodules but not bilateral acoustic schwannomas; VHL causes hemangioblastomas and clear cell RCC; PTEN mutations cause Cowden syndrome.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.