The reference OMIM entry for this protein is 603233

Pseudohypoparathyroidism, type ib; php1b
Php ib

A number sign (#) is used with this entry because pseudohypoparathyroidism type Ib (PHP Ib) is caused by deletions in the differentially methylated region (DMR) of the GNAS (139320) locus. One deletion (139320.0031) removes the entire NESP55 DMR and exons 3 and 4 of the antisense transcript of the GNAS gene (GNASAS; 610540.0001). PHP1B can also result from deletion in the STX gene (603666), a long-range control element of methylation at the GNAS locus. These methylation and imprinting defects result in the absence of expression of the maternal Gs-alpha isoform.

DESCRIPTION

Pseudohypoparathyroidism refers to a heterogeneous group of disorders characterized by resistance to parathyroid hormone (PTH; 168450). Pseudohypoparathyroidism type Ib is characterized clinically by isolated renal PTH resistance manifest as hypocalcemia, hyperphosphatemia, and increased serum PTH. Biochemical studies show a decreased response of urinary cAMP to exogenous PTH, but normal Gs activity in erythrocytes because the defect is restricted to renal tubule cells. In contrast to the findings in PHP Ia, patients with PHP Ib usually lack the physical characteristics of Albright hereditary osteodystrophy (AHO) and typically show no other endocrine abnormalities, although resistance to thyroid-stimulating hormone (TSH; 188540) has been reported in PHP Ib (Levine et al., 1983, Heinsimer et al., 1984). However, patients with PHP Ib may rarely show some features of AHO (Mariot et al., 2008). For a general phenotypic description, classification, and a discussion of molecular genetics of pseudohypoparathyroidism, see PHP1A (103580).

CLINICAL FEATURES

Frame et al. (1972) reported 2 patients with renal resistance to parathyroid hormone characterized by hypocalcemia and hyperphosphatemia and associated with osteitis fibrosa cystica. Frame et al. (1972) postulated that renal PTH resistance was the primary defect and that a secondary hyperparathyroid state occurred to cause the skeletal changes of osteitis fibrosa. The calcemic effect of both endogenous and exogenous PTH was blunted by the presence of hyperphosphatemia. Farfel and Bourne (1980) reported a family in which 5 patients with PHP type I had no signs of AHO and showed normal erythrocyte Gs protein activity. Kidd et al. (1980) described 3 patients with PHP and bone findings consistent with hyperparathyroidism, including elevated serum alkaline phosphatase and subperiosteal resorption on skeletal films. None of the patients had AHO features of short stature, brachydactyly, or mental deficiency. The authors commented on the paradoxic occurrence of hyperparathyroid bone disease in PHP, and suggested that this was an extreme of a clinical spectrum of skeletal responsiveness to excess PTH. Heinsimer et al. (1984) found that beta-adrenergic agonist-specific binding properties of red cell membranes were 45% of controls in 5 patients with PHP Ia and 97% of controls in 5 patients with PHP Ib. Further studies were consistent with a single defect causing deficient hormone receptor-nucleotide complex formation and adenylate cyclase activity in PHP Ia, whereas the biochemical lesion(s) appeared not to affect the complex formation in PHP Ib. Liu et al. (2000) studied 13 patients with PHP Ib, all of whom initially presented with hypocalcemia, hyperphosphatemia, and elevated serum PTH levels in the absence of renal insufficiency or any of the clinical or radiologic features of Albright hereditary osteodystrophy ... More on the omim web site

Subscribe to this protein entry history

Dec. 10, 2018: Protein entry updated
Automatic update: model status changed

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for STX16

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603233 was added.