title: Two mutations of the Gsalpha gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia.
abstract: Pseudohypoparathyroidism Ia (PHP-Ia), is an inherited disease with clinical hypoparathyroidism caused by parathyroid hormone resistance (PTH), and shows the phenotype of Albright hereditary osteodystrophy (AHO), including short stature, obesity, round face, brachydactyly, and subcutaneous ossification. This disease is caused by mutation that inactivates the alpha-subunit of Gs, the stimulatory regulator of adenylyl cyclase. Here, a novel frameshift mutation (delG at codon 88) in exon 4, and a missense mutation (R231H) in exon 9 of the Gsalpha gene were identified in two Japanese patients with sporadic PHP-Ia. Deletion of a G in exon 4 at codon 88 in the first patient produced a premature stop codon, resulting in the truncated protein. The second patient had a previously reported R231H mutation. Because this amino acid is located in a region, switch 2, that is thought to interact with the betagamma subunit of Gsalpha protein, this mutation may impair Gs protein function. We report here one novel Gsalpha mutation, and note that mutations in Japanese patients with PHP-Ia are probably heterogeneous.
authors.affiliation: Department of Pediatrics, Kushiro Red Cross Hospital, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: T
authors.initials: T
authors.lastname: Tajima
authors.forename: J
authors.initials: J
authors.lastname: Nakae
authors.forename: T
authors.initials: T
authors.lastname: Nagashima
authors.forename: K
authors.initials: K
authors.lastname: Satoh
authors.forename: K
authors.initials: K
authors.lastname: Okuhara
authors.forename: K
authors.initials: K
authors.lastname: Fujieda
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D018388:Codon, Terminator / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D007564:Japan; D008297:Male; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D011547:Pseudohypoparathyroidism / Q000235:genetics* / Q000503:physiopathology
chemical_list: D018388:Codon, Terminator; D019205:GTP-Binding Protein alpha Subunits, Gs