Absence of mutations in parathyroid hormone (PTH)/PTH-related protein receptor complementary deoxyribonucleic acid in patients with pseudohypoparathyroidism type Ib.

To clarify the mechanism of resistance to PTH in patients with pseudohypoparathyroidism (PHP) type Ib, the complementary DNA (cDNA) for PTH/PTH-related protein (PTHrP) receptor was analyzed in skin fibroblasts from three patients with PHP Ib and compared with those from a patient with PHP Ia and a normal subject. We have divided the full coding region of PTH/PTHrP receptor cDNA into five parts and amplified the cDNA by reverse transcription-coupled PCR. There was no difference in the size of PCR products among these patients and the normal control. Single strand conformation polymorphism analysis of the PCR products also showed no aberrant bands in PHP Ib patients. Furthermore, no mutation in PTH/PTHrP receptor cDNA was found by direct sequencing of the PCR products from these patients. These results demonstrate that there is no mutation in PTH/PTHrP receptor cDNA from skin fibroblasts at least in the examined patients with PHP Ib. In addition, the expression of PTH/PTHrP receptor messenger ribonucleic acid was reduced in two patients but was increased in one patient with PHP Ib, suggesting that a reduction in PTH/PTHrP receptor expression cannot explain the resistance to PTH in all patients with PHP Ib. Elucidation of the pathogenesis of PHP Ib may require examination of tissue-specific abnormality in the PTH signal transduction system in the kidney.