Albright hereditary osteodystrophy follows which inheritance pattern and mechanism?

• A. Autosomal recessive with PTH resistance
• B. X-linked with GNAS
• C. Autosomal dominant with GNAS mutation causing PTH resistance
• D. Mitochondrial inheritance

Answer: (C)

Albright hereditary osteodystrophy comes from a mutation in the GNAS gene, which encodes the Gs alpha subunit that links hormone receptors like the PTH receptor to adenylyl cyclase and cAMP production. When this signaling is impaired, target tissues don’t respond properly to PTH, leading to PTH resistance in the kidneys and the characteristic metabolic pattern.

The trait is inherited in an autosomal dominant fashion, because a single mutant GNAS allele can produce the phenotype. However, there is a parent-of-origin effect due to imprinting: if the mutated allele is inherited from the mother, PTH resistance is present (pseudohypoparathyroidism type Ia) alongside the Albright phenotypic features; if it’s inherited from the father, you can have the physical features without PTH resistance (pseudo-pseudohypoparathyroidism).