title: A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia.
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.
authors.affiliation: Department of Medicine, Massachusetts General Hospital 02114, USA.
authors.forename: E
authors.initials: E
authors.lastname: Schipani
authors.forename: K
authors.initials: K
authors.lastname: Kruse
authors.forename: H
authors.initials: H
authors.lastname: Jüppner
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004252:DNA Mutational Analysis; D004392:Dwarfism / Q000235:genetics*; D005260:Female; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010009:Osteochondrodysplasias / Q000235:genetics*; D017354:Point Mutation; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection
chemical_list: D007295:Inositol Phosphates; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone; D011994:Recombinant Proteins; D000242:Cyclic AMP