, Volume 37, Issue 3, pp 408–414 | Cite as

Clinical and genetic characterization of Portuguese patients with pseudohypoparathyroidism type Ib

  • Branca Maria CavacoEmail author
  • Rute Alexandra Tomaz
  • Fernando Fonseca
  • Mário Rui Mascarenhas
  • Valeriano Leite
  • Luís Gonçalves Sobrinho
Original Article


Patients with pseudohypoparathyroidism type Ib (PHP-Ib) present hypocalcemia and hyperphosphatemia, as a consequence of a resistance to PTH action, through its G-protein-coupled receptor, in the renal tubules. This resistance results from tissue-specific silencing of the G-protein alpha-subunit (Gsα), due to imprinting disruption of its encoding locusGNAS. In familial PHP-Ib, maternally inherited deletions at the STX16 gene are associated to a regional GNAS methylation defect. In sporadic PHP-Ib, broad methylation changes at GNAS arise from unknown genetic causes. In this study, we describe the clinical presentation of PHP-Ib in four Portuguese patients (two of whom were siblings), and provide further insight for the management of patients with this disease. The diagnosis of PHP-Ib was made after detection of GNAS imprinting defects in each of the cases. In the siblings, a regional GNAS methylation change resulted from a known 3.0 kb STX16 deletion. In the other two patients, the broad methylation defects at GNAS, which were absent in their relatives, resulted from genetic alterations that remain to be identified. We report the first clinical and genetic study of Portuguese patients with PHP-Ib. The genetic identification of a hereditary form of this rare disease allowed an early diagnosis, and may prevent hypocalcemia-related complications.


Genomic Imprinting Gsα Hypocalcemia Pseudohypoparathyroidism Syntaxin 16 



The authors are grateful to the families for their cooperation. This work was supported by Associação de Endocrinologia Oncológica.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Branca Maria Cavaco
    • 1
    • 5
    Email author
  • Rute Alexandra Tomaz
    • 1
    • 5
  • Fernando Fonseca
    • 2
  • Mário Rui Mascarenhas
    • 3
  • Valeriano Leite
    • 1
    • 4
    • 5
  • Luís Gonçalves Sobrinho
    • 4
    • 5
  1. 1.Centro de Investigação de Patobiologia Molecular, CIPMInstituto Português de Oncologia de Lisboa Francisco GentilLisbonPortugal
  2. 2.Serviço de EndocrinologiaHospital Curry CabralLisbonPortugal
  3. 3.Clínica Universitária de EndocrinologiaFaculdade de Medicina de LisboaLisbonPortugal
  4. 4.Serviço de EndocrinologiaInstituto Português de Oncologia de Lisboa Francisco GentilLisbonPortugal
  5. 5.Centro de Estudos de Doenças Crónicas, CEDOC, Faculdade de Ciências MédicasUniversidade Nova de LisboaLisbonPortugal

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