A 10-year-old child has multiple café-au-lait spots (>6, >5 mm diameter), axillary freckling, and bilateral optic nerve gliomas. This is neurofibromatosis type 1 (NF1). The NF1 gene product neurofibromin functions as:

• A Proto-oncogene that directly stimulates cell proliferation
• B Tumor suppressor that activates RAS GTPase activity (GAP protein), thereby inactivating RAS ✓
• C DNA repair enzyme preventing chromosomal instability
• D Cell adhesion molecule preventing tumor metastasis

Explanation

Neurofibromin (NF1 gene product) is a GTPase-activating protein (GAP) that accelerates the hydrolysis of RAS-GTP to RAS-GDP, thereby inactivating RAS and reducing downstream proliferative signaling through MAPK/ERK. Loss of neurofibromin (NF1 mutation — autosomal dominant, chromosome 17q11.2) leads to uncontrolled RAS activity and cell proliferation. This explains the tumor predisposition (neurofibromas, optic gliomas, malignant peripheral nerve sheath tumors). The two-hit hypothesis applies — germline mutation plus somatic second hit.

Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.