CALCIUM-SENSING RECEPTOR MUTATIONS IN FAMILIAL BENIGN HYPERCALCEMIA AND NEONATAL HYPERPARATHYROIDISM

Citation
Shs. Pearce et al., CALCIUM-SENSING RECEPTOR MUTATIONS IN FAMILIAL BENIGN HYPERCALCEMIA AND NEONATAL HYPERPARATHYROIDISM, The Journal of clinical investigation, 96(6), 1995, pp. 2683-2692
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
0021-9738
Volume
96
Issue
6
Year of publication
1995
Pages
2683 - 2692
Database
ISI
SICI code
0021-9738(1995)96:6<2683:CRMIFB>2.0.ZU;2-O
Abstract
Familial benign hypercalcemia (FBH) and neonatal hyperparathyroidism ( NHPT) are disorders of calcium homeostasis that are associated with mi ssense mutations of the calcium-sensing receptor (CaR). We have undert aken studies to characterize such CaR mutations in FBH and NHPT and to explore methods for their more rapid detection. Nine unrelated kindre ds (39 affected, 32 unaffected members) with FBH and three unrelated c hildren with sporadic NHPT were investigated for mutations in the 3,23 4-bp coding region of the CaR gene by DNA sequencing. Six novel hetero zygous (one nonsense and five missense) mutations were identified in s ix of the nine PBH kindreds, and two de novo heterozygous missense mut ations and one homozygous frame-shift mutation were identified in the three children with NHPT. Our results expand the phenotypes associated with CaR mutations to include sporadic NHPT, Single-stranded conforma tional polymorphism analysis was found to be a sensitive and specific mutational screening method that detected > 85% of these CaR gene muta tions. The single-stranded conformational polymorphism identification of CaR mutations may help in the distinction of FBH from mild primary hyperparathyroidism which can be clinically difficult. Thus, the resul ts of our study will help to supplement the clinical evaluation of som e hypercalcemic patients and to elucidate further the structure-functi on relationships of the CaR.