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 patient with this disorder and identified a novel 4-base pair deletion in exon 7 in codons 189-190. This deletion causes a frameshift and if synthesis of a truncated form of Gs alpha occurred, it would likely be biologically inactive. The patient was heterozygous for this deletion. The patient's mother and an unaffected brother were tested for the presence of this mutation. His mother had the same mutation, and although her serum calcium and parathyroid hormone levels were within the normal range, she had subcutaneous calcifications. Thus, this mutation appears to be necessary but not sufficient to cause the complete pseudohypoparathyroidism phenotype and thus, other unknown factors, either genetic or acquired, may be necessary for the full syndrome to occur.
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