Two mutations of the Gs alpha gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia

Pseudohypoparathyroidism Ia (PHP-Ia), is an inherited disease with clinical hypoparathyroidism caused by parathyroid hormone resistance (PTH), and sho ws the phenotype of Albright hereditary osteodystrophy (AHO), including sho rt stature, obesity, round face, brachydactyly, and subcutaneous ossificati on. This disease is caused by mutation that inactivates the alpha -subunit of Gs, the stimulatory regulator of adenylyl cyclase. Here, a novel framesh ift mutation (delG at codon 88) in exon 4, and a missense mutation (R231H) in exon 9 of the Gs alpha gene were identified in two Japanese patients wit h sporadic PHP-Ia. Deletion of a G in exon 4 at codon 88 in the first patie nt produced a premature stop codon, resulting in the truncated protein. The second patient had a previously reported R231H mutation. Because this amin o acid is located in a region, switch 2, that is thought to interact with t he beta gamma subunit of Gs alpha protein, this mutation may impair Gs prot ein function. We report here one novel Gs alpha mutation, and note that mut ations in Japanese patients with PHP-Ia are probably heterogeneous.