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Pseudohypoparathyroidism Type Ib (PHP-Ib): PTH-Resistant Hypocalcemia and Hyperphosphatemia Due to Abnormal GNAS Methylation

  • Harald JüppnerEmail author
Chapter

Abstract

Pseudohypoparathyroidism type Ib (PHP-Ib) is a rare disorder characterized by PTH resistance in the proximal renal tubules, which leads to hypocalcemia, hyperphosphatemia, and an elevated serum PTH level. Resistance to other hormones that mediate their actions through G protein-coupled receptors and evidence for AHO can also be observed but are much less frequently than in pseudohypoparathyroidism type Ia (PHP-Ia). Most variants of PHP-Ib are associated with GNAS methylation changes, thereby reducing maternal expression of the stimulatory G protein (Gsα) in few tissues, where paternal expression of this signaling protein is silenced through as-of-yet unknown mechanisms. In familial PHP-Ib cases, these epigenetic changes are caused by deletions within or upstream of GNAS. Duplication of large portions of the paternal chromosome 20q is observed in a few patients with the sporadic form of the disease, but most of these PHP-Ib cases remain undefined at the molecular level.

Keywords

Proximal Renal Tubule GNAS Mutation Urinary Phosphate Excretion Sporadic Variant GNAS Locus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer-Verlag Italia 2015

Authors and Affiliations

  1. 1.Endocrine Unit and Pediatric Nephrology UnitMassachusetts General Hospital and Harvard Medical SchoolBostonUSA

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