Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites

Fadil Hannan, M Andrew Nesbit, Chen Zhang, Treena Cranston, Alan J Curley, Brian Harding, Carl Fratter, Nigel Rust, Paul T Christie, Jeremy J O Turner, Manuel C Lemos, Michael R Bowl, Roger Bouillon, Caroline Brain, Nicola Bridges, Christine Burren, John Connell, Heike Jung, Eileen Marks, David McCredieZulf Mughal, Christine P Rodda, Sherida Tollefsen, Edward M Brown, Jenny J Yang, Rajesh V Thakker

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100 Citations (Scopus)

Abstract

The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that has an extracellular bilobed venus flytrap domain (VFTD) predicted to contain five calcium (CA2+)-binding sites. To elucidate the structure-function relationships of the VFTD, we investigated 294 unrelated probands with familial hypocalciuric hypercalcaemia (FHH), neonatal severe primary hyperparathyroidism (NSHPT) or autosomal dominant hypo-calcaemic hupercalciuria (ADHH) for CaSR mutations and performed in vitro functional expression studies and three-dimensional modelling of mutations involving the VFTD.
Original languageEnglish
Pages (from-to)2768 - 2778
Number of pages11
JournalHuman Molecular Genetics
Volume21
Issue number12
DOIs
Publication statusPublished - 2012

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