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Hormones

, Volume 15, Issue 4, pp 557–559 | Cite as

A novel mutation of the calcium-sensing receptor gene in a German subject with familial hypocalciuric hypercalcemia and primary hyperparathyroidism

  • Marios Papadakis
  • Natalie Meurer
  • Theodora Margariti
  • Anke Meyer
  • Norbert Weyerbrock
  • Cornelia Dotzenrath
Case report

Abstract

OBJECTIVE

The coexistence of familial hypocalciuric hypercalcemia (FHH) and primary hyperparathyroidism (PHPT) is extremely rare. Genetic evidence has demonstrated a causal relationship between FHH and the presence of inactivating mutations in the calcium-sensing receptor gene.

METHOD

We herein report a 60-year-old German patient who was referred for hypercalcemia and increased PTH levels found incidentally during normal routine blood tests.

RESULTS

The patient underwent surgical exploration and the diagnosis of PHPT was histologically confirmed. One week later, the follow-up blood tests revealed recurrent hypercalcemia, and the possibility of FHH was reconsidered. Genetic analysis was performed and revealed a novel heterozygous CaSR single missense mutation (Arg551Gly) within the extracellular CaSR domain.

CONCLUSION

We report a novel heterozygous missense inactivating mutation within the extracellular CaSR domain in a German subject with FHH and histologically proven PHPT.

Key words

Calcium-sensing receptor Familial hypocalciuric hypercalcemia Missense mutation Primary hyperparathyroidism 

References

  1. 1.
    Christensen SE, Nissen PH, Vestergaard P, Mosekilde L, 2011 Familial hypocalciuric hypercalcaemia: a review. Curr Opin Endocrinol Diabetes Obes 18: 359–370.CrossRefGoogle Scholar
  2. 2.
    Al-Salameh A, Cetani F, Pardi E, et al, 2011 A novel mutation in the calcium-sensing receptor in a French family with familial hypocalciuric hypercalcaemia. Eur J Endocrinol 165: 359–363.CrossRefGoogle Scholar
  3. 3.
    Glendenning P, 2003 Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century. Clin Biochem Rev 24: 27–30.PubMedCentralGoogle Scholar
  4. 4.
    Nakayama T, Minato M, Nakagawa M, et al, 2001 A novel mutation in Ca2+-sensing receptor gene in familial hypocalciuric hypercalcemia. Endocr 15: 277–282.CrossRefGoogle Scholar
  5. 5.
    Zapanti E, Polonifi A, Kokkinos M, et al, 2015 A novel mutation of the calcium-sensing receptor gene in a Greek family from Nisyros. Hormones (Athens) 14: 321–325.CrossRefGoogle Scholar
  6. 6.
    Tõke J, Czirják G, Patócs A, et al, 2007 Neonatal severe hyperparathyroidism associated with a novel de novo heterozygous R551K inactivating mutation and a heterozygous A986S polymorphism of the calcium-sensing receptor gene. Clin Endocrinol (Oxf) 67: 385–392.CrossRefGoogle Scholar
  7. 7.
    D’Souza-Li L, Yang B, Canaff L, et al, 2002 Identification and functional characterization of novel calcium-sensing receptor mutations in familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia. J Clin Endocrinol Metab 87: 1309–1318.CrossRefGoogle Scholar
  8. 8.
    Nissen PH, Christensen SE, Heickendorff L, Brixen K, Mosekilde L, 2007 Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population. J Clin Endocrinol Metab 92: 4373–4379.CrossRefGoogle Scholar
  9. 9.
    Schwarz P, Larsen NE, Lønborg Friis IM, Lillquist K, Brown EM, Gammeltoft S, 2000 Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism associated with mutations in the human Ca2+-sensing receptor gene in three Danish families. Scand J Clin Lab Invest 60: 221–227.CrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2016

Authors and Affiliations

  • Marios Papadakis
    • 1
    • 2
  • Natalie Meurer
    • 1
  • Theodora Margariti
    • 1
  • Anke Meyer
    • 1
  • Norbert Weyerbrock
    • 1
  • Cornelia Dotzenrath
    • 1
  1. 1.Department of Endocrine Surgery, Helios ClinicUniversity Hospital Witten-HerdeckeWuppertalGermany
  2. 2.Department of Plastic and Hand SurgeryHelios Clinic, University Hospital Witten-HerdeckeWuppertalGermany

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