A patient is found to have pseudohypoparathyroidism type 1a (Albright's hereditary osteodystrophy). The molecular defect is a loss-of-function mutation in:

• A Gsα protein (GNAS gene) ✓
• B PTH receptor (PTH1R) extracellular domain
• C Adenylyl cyclase catalytic subunit
• D Phosphodiesterase type 4

Explanation

Pseudohypoparathyroidism type 1a results from a heterozygous loss-of-function mutation in GNAS encoding Gsα. Despite normal or elevated PTH, the PTH signal cannot be transduced because Gsα is non-functional, leading to blunted adenylyl cyclase activation. Clinically, hypocalcemia and hyperphosphatemia occur with elevated PTH levels (PTH resistance). The same Gsα defect causes resistance to other Gs-coupled hormone receptors (TSH, LH, FSH). PTH1R mutations cause a distinct condition. Adenylyl cyclase mutations and phosphodiesterase mutations are not responsible for this syndrome.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.