Genetic Testing in Pseudohypoparathyroidism

  • Agnès LinglartEmail author
  • Susanne Thiele


Pseudohypoparathyroidism (PHP) is the consequence of the lack of the parathyroid hormone (PTH) receptor (PTHR1) activation by its ligand, PTH. So far, most of the identified causes of PHP affect the proper signaling of the PTHR1 through the Gsa/cAMP/PKA pathway. Because of the phenotype overlap of the different forms of PHPs, genetic testing highly depends on symptoms and biochemistry of the affected patient. Maternal loss-of-function mutations of Gsa, heterozygous mutations of PRKAR1A, and imprinting defects of GNAS have been identified in patients with PTH resistance and Albright osteodystrophy. Paternal loss-of-function mutations of Gsa and heterozygous mutations of PDE4D have been identified in patients with a predominant bone phenotype resembling Albright osteodystrophy. In vivo infusion of PTH, in vitro assay of Gsa bioactivity, and a wide range of genomic and epigenomic investigations have been designed to apprehend the molecular basis of PHP.


Pseudohypoparathyroidism GNAS Isodisomy Acrodysostosis Imprinting 


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© Springer-Verlag Italia 2015

Authors and Affiliations

  1. 1.Department of Pediatric EndocrinologyCenter of Reference for Rare Disorders of the Calcium and Phosphorus Metabolism, APHP, Paris-Sud Hospital and Paris-Sud UniversityLe Kremlin BicêtreFrance
  2. 2.Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent MedicineUniversity of LuebeckLuebeckGermany

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