Localization of familial benign hypercalcemia, Oklahoma variant (FBH(Ok)), to chromosome 19q13

Sarah E. Lloyd, Anna A.J. Pannett, Peter H. Dixon, Michael P. Whyte, Rajesh V. Thakker

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

Calcium homeostasis by the kidneys and parathyroids is mediated by the calcium-sensing receptor (CaSR), which is located on 3q21-q24 and belongs to family C of the superfamily of G-protein coupled receptors that includes those for metabotropic glutamate, certain pheromones, and γ-amino butyric acid (GABA-B). Inactivating CaSR mutations result in familial benign hypercalcemia (FBH), or familial hypocalciuric hypercalcemia (FHH), whereas activating mutations result in hypocalcemic hypercalciuria. However, not all FBH patients have CaSR mutations, which, together with the mapping of another FBH locus to 19p13.3, suggests that additional CaSRs or second messengers may be involved. These may be identified by positional cloning, and we therefore performed a genomewide search, using chromosome-specific sets of microsatellite polymorphisms, in an Oklahoma family with an FBH variant (FBH(Ok)), for which linkage to 3q and 19p had been excluded. Linkage was established between FBH(Ok) and eight chromosome 19q13 loci, with the highest LOD score, 6.67 (recombination fraction .00), obtained with D19S606. Recombinants further mapped FBH(Ok)) to a <12-cM interval flanked by D19S908 and D19S866. The calmodulin III gene is located within this interval, and DNA sequence analysis of the coding region, the 5' UTR, and part of the promoter region in an individual affected with FBH(Ok) did not detect any abnormalities, thereby indicating that this gene is unlikely to be implicated in the etiology of FBH(Ok). This mapping of FBH(Ok) to chromosome 19q13 will facilitate the identification of another CaSR or a mediator of calcium homeostasis.

Original languageEnglish
Pages (from-to)189-195
Number of pages7
JournalAmerican journal of human genetics
Volume64
Issue number1
DOIs
StatePublished - 1999

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