caa a22 4500 397573774 CHVBK 20180308164849.0 cr unu---uuuuu 161202e199605 xx s 000 0 eng 10.1093/hmg/5.5.601 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.5.601 Mutations in the Ca2+-Sensing Receptor Gene Cause Autosomal Dominant and Sporadic Hypoparathyroidism [Elektronische Daten] [Jeffrey Baron, Karen K. Winer, Jack A. Yanovski, Adrienne W. Cunningham, Louisa Laue, Donald Zimmerman, Gordon B. Cutler] Parathyroid hormone secretion is negatively regulated by a 7-transmembrane domain, G-protein coupled Ca2+-sensing receptor. We hypothesized that activating mutations in this receptor might cause autosomal dominant hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified, in two families with ADHP, heterozygous missense mutations in the Ca2+-sensing receptor gene that cosegregated with the disorder. None of 50 normal controls had either mutation. We also identified a de novo, missense Ca2+-sensing receptor mutation in a child with severe sporadic hypoparathyroidism. The amino acid substitution in one ADHP family affected the N-terminal, extracellular domain of the receptor. The other mutations involved the transmembrane region. Unlike patients with acquired hypoparathyroidism, patients with these mutations had hypercalciuria even at low serum calcium concentrations. Their greater hypercalciuria presumably reflected activation of Ca2+-sensing receptors in kidney cells, where the receptor negatively regulates calcium reabsorption. This augmented hypercalciuria increases the risk of renal complications and thus has implications for the choice of therapy. © 1996 Oxford University Press Baron Jeffrey Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10 Room 10N262, National Institutes of Health, 10 Center Dr MSC 1862, Bethesda, MD 20892-1862, USA aut Winer Karen K. Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10 Room 10N262, National Institutes of Health, 10 Center Dr MSC 1862, Bethesda, MD 20892-1862, USA aut Yanovski Jack A. Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10 Room 10N262, National Institutes of Health, 10 Center Dr MSC 1862, Bethesda, MD 20892-1862, USA aut Cunningham Adrienne W. Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10 Room 10N262, National Institutes of Health, 10 Center Dr MSC 1862, Bethesda, MD 20892-1862, USA aut Laue Louisa Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10 Room 10N262, National Institutes of Health, 10 Center Dr MSC 1862, Bethesda, MD 20892-1862, USA aut Zimmerman Donald Department of Pediatrics, Mayo Clinic, 200 First Street, S.W., Rochester, MN 55905, USA aut Cutler Gordon B. Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10 Room 10N262, National Institutes of Health, 10 Center Dr MSC 1862, Bethesda, MD 20892-1862, USA aut Human Molecular Genetics Oxford University Press 5/5(1996-05), 601-606 0964-6906 5:5<601 1996 5 hmg https://doi.org/10.1093/hmg/5.5.601 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.5.601 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Baron Jeffrey Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10 Room 10N262, National Institutes of Health, 10 Center Dr MSC 1862, Bethesda, MD 20892-1862, USA aut NATIONALLICENCE 700 1- Winer Karen K. Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10 Room 10N262, National Institutes of Health, 10 Center Dr MSC 1862, Bethesda, MD 20892-1862, USA aut NATIONALLICENCE 700 1- Yanovski Jack A. Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10 Room 10N262, National Institutes of Health, 10 Center Dr MSC 1862, Bethesda, MD 20892-1862, USA aut NATIONALLICENCE 700 1- Cunningham Adrienne W. Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10 Room 10N262, National Institutes of Health, 10 Center Dr MSC 1862, Bethesda, MD 20892-1862, USA aut NATIONALLICENCE 700 1- Laue Louisa Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10 Room 10N262, National Institutes of Health, 10 Center Dr MSC 1862, Bethesda, MD 20892-1862, USA aut NATIONALLICENCE 700 1- Zimmerman Donald Department of Pediatrics, Mayo Clinic, 200 First Street, S.W., Rochester, MN 55905, USA aut NATIONALLICENCE 700 1- Cutler Gordon B. Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Building 10 Room 10N262, National Institutes of Health, 10 Center Dr MSC 1862, Bethesda, MD 20892-1862, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/5(1996-05), 601-606 0964-6906 5:5<601 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford