An update on the clinical and molecular characteristics of pseudohypoparathyroidism

Michael A. Levine

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE OF REVIEW: To provide the reader with a review of contemporary literature describing the evolving understanding of the molecular pathobiology of pseudohypoparathyroidism (PHP). RECENT FINDINGS: The features of PHP type 1 reflect imprinting of the GNAS gene, which encodes the α subunit of the heterotrimeric G protein (Gαs) that couples heptahelical receptors to activation of adenylyl cyclase. Transcription of Gαs is biallelic in most cells, but is primarily from the maternal allele in some tissues (e.g. proximal renal tubules, thyroid, pituitary somatotropes, gonads). Patients with PHP 1a have heterozygous mutations within the exons of the maternal GNAS allele that encode Gαs, whereas patients with PHP 1b have methylation defects in the GNAS locus that reduce transcription of Gαs from the maternal allele. In both PHP 1a and PHP 1b, paternal imprinting of Gαs leads to resistance to parathyroid hormone and TSH. Although brachydactyly is characteristic of PHP 1a, it is sometimes present in patients with PHP 1b. SUMMARY: Molecular studies enable a distinction between PHP 1a and PHP 1b, with different mechanisms accounting for Gαs deficiency. Clinical overlap between these two forms of PHP type 1 is likely due to the variable levels of Gαs activity expressed in specific cell types.

Original languageEnglish (US)
Pages (from-to)443-451
Number of pages9
JournalCurrent Opinion in Endocrinology, Diabetes and Obesity
Volume19
Issue number6
DOIs
StatePublished - Dec 2012
Externally publishedYes

Keywords

  • GNAS
  • hormone resistance
  • imprinting

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine
  • Nutrition and Dietetics

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