A 4-BASE PAIR DELETION MUTATION OF GS-ALPHA GENE IN A JAPANESE PATIENT WITH PSEUDOHYPOPARATHYROIDISM

Mutations in the guanine nucleotide binding protein alpha subunit (Gs alpha) have been found in patients with pseudohypoparathyroidism (PHP) . We have screened the Gs alpha gene for mutations in a Japanese patie nt with this disorder and identified a novel 4-base pair deletion in e xon 7 in codons 189-190. This deletion causes a frameshift and if synt hesis of a truncated form of Gs alpha occurred, it would likely be bio logically inactive. The patient was heterozygous for this deletion. Th e patient's mother and an unaffected brother were tested for the prese nce of this mutation. His mother had the same mutation, and although h er serum calcium and parathyroid hormone levels were within the normal range, she had subcutaneous calcifications. Thus, this mutation appea rs to be necessary but not sufficient to cause the complete pseudohypo parathyroidism phenotype and thus, other unknown factors, either genet ic or acquired, may be necessary for the full syndrome to occur.