A Constitutively Active Mutant PTH-PTHrP Receptor in Jansen-Type Metaphyseal Chondrodysplasia
- 7 April 1995
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 268 (5207) , 98-100
- https://doi.org/10.1126/science.7701349
Abstract
A single heterozygous nucleotide exchange in exon M2 of the gene encoding the parathyroid hormone-parathyroid hormone-related peptide (PTH-PTHrP) receptor was identified in a patient with Jansen-type metaphyseal chondrodysplasia, which changes a strictly conserved histidine residue at position 223 in the receptor's first intracellular loop to arginine. Constitutive, ligand-independent adenosine 3′,5′-monophosphate accumulation was observed in COS-7 cells expressing the mutant PTH-PTHrP receptor but not in cells expressing the wild-type receptor. This finding explains the severe ligand-independent hypercalcemia and hypophosphatemia, and most likely the abnormal formation of endochondral bone, in this rare form of short-limbed dwarfism.Keywords
This publication has 16 references indexed in Scilit:
- Autosomal dominant hypocalcaemia caused by a Ca2+-sensing receptor gene mutationNature Genetics, 1994
- Parathyroid hormone-related peptide-depleted mice show abnormal epiphyseal cartilage development and altered endochondral bone formation.The Journal of cell biology, 1994
- Germline mutations in the thyrotropin receptor gene cause non–autoimmune autosomal dominant hyperthyroidismNature Genetics, 1994
- Lethal skeletal dysplasia from targeted disruption of the parathyroid hormone-related peptide gene.Genes & Development, 1994
- Calcium metabolism in the jansen type of metaphyseal dysplasiaEuropean Journal of Pediatrics, 1993
- A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious pubertyNature, 1993
- Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomasNature, 1993
- Heterozygous missense mutation in the rhodopsin gene as a cause of congenital stationary night blindnessNature Genetics, 1993
- Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor functionCell, 1993
- Constitutively active mutants of rhodopsinNeuron, 1992