A patient with McCune-Albright syndrome has autonomous hormone hypersecretion in multiple endocrine glands without ligand stimulation. The molecular defect is a gain-of-function mutation in which protein?

• A Receptor tyrosine kinase (RTK)
• B Adenylyl cyclase catalytic subunit
• C Phospholipase C-beta
• D Gs-alpha subunit of the heterotrimeric G-protein ✓

Explanation

McCune-Albright syndrome results from a somatic activating (gain-of-function) mutation in GNAS1, encoding the Gs-alpha subunit. The mutated Gs-alpha has impaired intrinsic GTPase activity, causing it to remain in the active GTP-bound state continuously, leading to constitutive adenylyl cyclase stimulation, elevated cAMP, and autonomous activation of cAMP-dependent (PKA-mediated) hormone secretion in affected tissues (thyroid, adrenal, gonads, pituitary). Adenylyl cyclase itself is not mutated; it is downstream of Gs-alpha.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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