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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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

Cite this

Hannan, Fadil ; Nesbit, M Andrew ; Zhang, Chen ; Cranston, Treena ; Curley, Alan J ; Harding, Brian ; Fratter, Carl ; Rust, Nigel ; Christie, Paul T ; Turner, Jeremy J O ; Lemos, Manuel C ; Bowl, Michael R ; Bouillon, Roger ; Brain, Caroline ; Bridges, Nicola ; Burren, Christine ; Connell, John ; Jung, Heike ; Marks, Eileen ; McCredie, David ; Mughal, Zulf ; Rodda, Christine P ; Tollefsen, Sherida ; Brown, Edward M ; Yang, Jenny J ; Thakker, Rajesh V. / Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites. In: Human Molecular Genetics. 2012 ; Vol. 21, No. 12. pp. 2768 - 2778.
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title = "Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites",
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.",
author = "Fadil Hannan and Nesbit, {M Andrew} and Chen Zhang and Treena Cranston and Curley, {Alan J} and Brian Harding and Carl Fratter and Nigel Rust and Christie, {Paul T} and Turner, {Jeremy J O} and Lemos, {Manuel C} and Bowl, {Michael R} and Roger Bouillon and Caroline Brain and Nicola Bridges and Christine Burren and John Connell and Heike Jung and Eileen Marks and David McCredie and Zulf Mughal and Rodda, {Christine P} and Sherida Tollefsen and Brown, {Edward M} and Yang, {Jenny J} and Thakker, {Rajesh V}",
year = "2012",
doi = "10.1093/hmg/dds105",
language = "English",
volume = "21",
pages = "2768 -- 2778",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
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Hannan, F, Nesbit, MA, Zhang, C, Cranston, T, Curley, AJ, Harding, B, Fratter, C, Rust, N, Christie, PT, Turner, JJO, Lemos, MC, Bowl, MR, Bouillon, R, Brain, C, Bridges, N, Burren, C, Connell, J, Jung, H, Marks, E, McCredie, D, Mughal, Z, Rodda, CP, Tollefsen, S, Brown, EM, Yang, JJ & Thakker, RV 2012, 'Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites', Human Molecular Genetics, vol. 21, no. 12, pp. 2768 - 2778. https://doi.org/10.1093/hmg/dds105

Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites. / Hannan, Fadil; Nesbit, M Andrew; Zhang, Chen; Cranston, Treena; Curley, Alan J; Harding, Brian; Fratter, Carl; Rust, Nigel; Christie, Paul T; Turner, Jeremy J O; Lemos, Manuel C; Bowl, Michael R; Bouillon, Roger; Brain, Caroline; Bridges, Nicola; Burren, Christine; Connell, John; Jung, Heike; Marks, Eileen; McCredie, David; Mughal, Zulf; Rodda, Christine P; Tollefsen, Sherida; Brown, Edward M; Yang, Jenny J; Thakker, Rajesh V.

In: Human Molecular Genetics, Vol. 21, No. 12, 2012, p. 2768 - 2778.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites

AU - Hannan, Fadil

AU - Nesbit, M Andrew

AU - Zhang, Chen

AU - Cranston, Treena

AU - Curley, Alan J

AU - Harding, Brian

AU - Fratter, Carl

AU - Rust, Nigel

AU - Christie, Paul T

AU - Turner, Jeremy J O

AU - Lemos, Manuel C

AU - Bowl, Michael R

AU - Bouillon, Roger

AU - Brain, Caroline

AU - Bridges, Nicola

AU - Burren, Christine

AU - Connell, John

AU - Jung, Heike

AU - Marks, Eileen

AU - McCredie, David

AU - Mughal, Zulf

AU - Rodda, Christine P

AU - Tollefsen, Sherida

AU - Brown, Edward M

AU - Yang, Jenny J

AU - Thakker, Rajesh V

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

UR - http://hmg.oxfordjournals.org/content/21/12/2768.full.pdf

U2 - 10.1093/hmg/dds105

DO - 10.1093/hmg/dds105

M3 - Article

VL - 21

SP - 2768

EP - 2778

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 12

ER -