CASR gene activating mutations in two families with autosomal dominant hypocalcemia

Vito Guarnieri, Angela Valentina D'Elia, Filomena Baorda, Valerio Pazienza, Giorgia Benegiamo, Pietro Stanziale, Massimiliano Copetti, Claudia Battista, Franco Grimaldi, Giuseppe Damante, Fabio Pellegrini, Leonardo D'Agruma, Leopoldo Zelante, Massimo Carella, Alfredo Scillitani

Research output: Contribution to journalArticlepeer-review


Background: Autosomal dominant hypocalcemia (ADH) is an endocrine disorder caused by activating mutations of the calcium-sensing receptor (CASR) gene which plays a major role in maintaining calcium homeostasis. Biochemical features of ADH are hypocalcemia and hypercalciuria with inappropriately low levels of parathyroid hormone (PTH). We report on two four-generation families affected by ADH. Aim: To identify mutations of CASR gene in subjects affected by familial idiopathic hypoparathyroidism. To perform functional assays of identified CASR variants by transient transfection on HEK293 cells. Results: We identified two CASR variants (Q681R and P221L): the Q681R variant was novel while the P221L had been previously published. Functional assays on the Q681R variant showed that it did not alter the whole expression nor the correct plasmamembrane localization, but enhanced the signaling function, increasing the sensitivity of the receptor as compared to the WT. Conclusions: We report two activating CASR mutations in two families affected by ADH and the functional assays performed on the novel variant Q681R. Our work enlarged the spectrum of mutations of the CASR and contributed to a better elucidation of the protein function.

Original languageEnglish
Pages (from-to)548-552
Number of pages5
JournalMolecular Genetics and Metabolism
Issue number3
Publication statusPublished - Nov 2012


  • ADH
  • CASR
  • Hypoparathyrodism
  • Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism


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