A 24-year-old woman has recurrent fractures and limb deformity. X-ray of the femur shows diffuse ground-glass lucency with endosteal scalloping and thinning of the cortex, plus a varus deformity of the femoral neck. She also has cafe-au-lait spots with irregular 'coast of Maine' borders and precocious puberty. The underlying genetic defect involves:
- A GNAS gene encoding the alpha subunit of Gs protein ✓
- B EXT1 or EXT2 genes encoding glycosyltransferases
- C APC gene on chromosome 5q
- D NF1 gene on chromosome 17
Correct answer: A. GNAS gene encoding the alpha subunit of Gs protein
Explanation
McCune-Albright syndrome comprises polyostotic fibrous dysplasia, cafe-au-lait macules with irregular borders, and endocrine hyperfunction such as precocious puberty. It results from a postzygotic activating mutation of the GNAS gene coding for Gs alpha, which also drives autonomous hormone secretion. EXT1/EXT2 mutations cause hereditary multiple exostoses (option B), NF1 causes neurofibromatosis type 1 with smooth-bordered cafe-au-lait spots, and APC is familial polyposis coli.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.