Prevalence of three mutations in the Gsα gene among 24 families with pseudohypoparathyroidism type Ia

Pseudohypoparathyroidism type Ia (PHP-Ia), an inherited multi-hormone resistance syndrome, is associated with deficient cellular activity of the alpha-subunit of the guanine nucleotide-binding protein (Gs alpha) that stimulates adenylyl cyclase. We determined prevalence of three recently described mutations in exons 1 and 10 of the Gs alpha gene among 24 unrelated patients with PHP-Ia. Restriction analysis was used to detect two mutations that produce unique RFLPs, and allele-specific oligonucleotide hybridization was used to detect the other mutation. As none of these mutations were not found, genomic DNA was analyzed with denaturing gradient gel electrophoresis to screen for other mutations in exon 10. Mutations of the initiation codon and exon 10 in the Gs alpha gene thus rarely (< or = 4% each) cause PHP-Ia and the Gs alpha gene mutations causing PHP-Ia are heterogeneous and unique to each pedigree.