Genetic basis for resistance to parathyroid hormone

Michael A. Levine, Emily Germain-Lee, Suzanne Jan De Beur

Research output: Contribution to journalArticle

Abstract

Pseudohypoparathyroidism (PHP) is associated with biochemical hypoparathyroidism (i.e. hypocalcemia and hyperphosphatemia) due to parathyroid hormone (PTH) resistance rather than to PTH deficiency. Patients with PHP type 1a have a generalized form of hormone resistance plus a constellation of developmental defects termed Albright hereditary osteodystrophy (AHO). Within PHP type 1a families some individuals will show AHO but have normal hormone responsiveness, a variant phenotype termed pseudo-PHP. By contrast, patients with PHP type 1b manifest only PTH resistance and lack features of AHO. These various forms of PHP are due to defects in the GNAS1 gene that lead to decreased expression or activity of the α-subunit of the stimulatory G protein (Gsα). Tissue-specific genomic imprinting of GNAS1 accounts for the variable phenotypes of patients with GNAS1 defects.

Original languageEnglish (US)
Pages (from-to)87-95
Number of pages9
JournalHormone Research
Volume60
Issue numberSUPPL. 3
DOIs
StatePublished - Dec 30 2003

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Keywords

  • G protein
  • Imprinting
  • Pseudohypoparathyroidism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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