Inactivating mutation in the human parathyroid hormone receptor type 1 gene in Blomstrand chondrodysplasia

Endocrinology. 1998 Dec;139(12):5255-8. doi: 10.1210/endo.139.12.6522.


A single homozygous nucleotide exchange in exon E3 of the gene encoding the parathyroid hormone receptor type 1 (PTHR1) was identified in an infant with Blomstrand chondrodysplasia born to consanguineous parents. This alteration changes a strictly conserved proline residue at position 132 in the receptor's amino terminal extracellular domain to leucine. COS-1 cells expressing the mutant receptor did not accumulate cyclic adenosine 3',5'-monophosphate in response to PTH or PTH-related peptide (PTHrP) and did not bind the radiolabeled ligand. Expression of the mutant protein on the cell surface of transiently transfected COS-1 cells and in growth plate chondrocytes derived from the affected infant suggests that proline 132 is critical for the receptor's intrinsic binding activity. These findings suggest that the Blomstrand form of human short-limbed dwarfism arises from defective PTHR1 signaling in the developing cartilaginous skeleton.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells / metabolism
  • Cell Membrane / metabolism
  • Chondrocytes / metabolism
  • Cyclic AMP / metabolism
  • Growth Plate / metabolism
  • Growth Plate / pathology
  • Humans
  • Immunohistochemistry
  • Infant, Newborn
  • Molecular Sequence Data
  • Mutation, Missense / genetics
  • Mutation, Missense / physiology*
  • Osteochondrodysplasias / genetics*
  • Parathyroid Hormone / pharmacology
  • Parathyroid Hormone-Related Protein
  • Proteins / pharmacology
  • Receptors, Parathyroid Hormone / chemistry
  • Receptors, Parathyroid Hormone / genetics*
  • Receptors, Parathyroid Hormone / metabolism


  • PTHLH protein, human
  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein
  • Proteins
  • Receptors, Parathyroid Hormone
  • Cyclic AMP