PSEUDOHYPOPARATHYROIDISM TYPE IA - 2 NEW HETEROZYGOUS FRAMESHIFT MUTATIONS IN EXON-5 AND EXON-10 OF THE GS-ALPHA GENE

Pseudohypoparathyroidism type Ia (PHP-Ia) is a hereditary disease char acterized by resistance to PTH and other hormones that act via cAMP. P atients have deficient activity of Gs alpha, the alpha subunit of the G protein, which couples hormone receptors to stimulation of adenylate cyclase, We describe two new mutations discovered in two sporadic pat ients with PHP-Ia. Using genomic DNA, we have amplified exons 2-13 of the Gs alpha gene (GNAS1) by PCR, and sequenced the resulting products . Both patients had Albright's hereditary osteodystrophy, resistance t o multiple hormones, and deficient Gs alpha activity. In the first pat ient, a deletion of a C in exon 5 at codon 115 was found. In the secon d patient, an insertion of a C in exon 10 at codon 267 was detected. B oth these heterozygous mutations cause frameshift, and predict decreas ed production of Gs alpha. This report adds two new Gs alpha mutations to the known ten mutations recently described.