Novel mutations in the parathyroid hormone (PTH)/PTH-related peptide receptor type 1 causing Blomstrand osteochondrodysplasia types I and II

J Clin Endocrinol Metab. 2007 Mar;92(3):1088-95. doi: 10.1210/jc.2006-0300. Epub 2006 Dec 12.


Context: The PTH/PTHrP receptor type 1 (PTHR1) has a key role in endochondral ossification, which is emphasized by diseases resulting from mutations in the PTHR1 gene. Among these diseases is Blomstrand osteochondrodysplasia (BOCD).

Objective: BOCD can be divided into two types, depending on the severity of the skeletal abnormalities. The molecular basis for this heterogenic presentation is unknown.

Design and patients: We performed mutation analysis in two families with type I and in three families with the less severe form of BOCD type II.

Results: In one of the type I BOCD cases, a homozygous nonsense mutation (R104X) was found, resulting in a truncated PTHR1. In the second type I BOCD case, no mutation was found. A homozygous nucleotide change (intron M4+27C>T) was demonstrated in one of the type II BOCD cases creating a novel splice site. In dermal fibroblasts of the patient, this novel splice site was preferentially used, resulting in an aberrant transcript. The wild-type transcript remained, however, present, albeit at low levels. In the other two families with type II BOCD, a previously identified homozygous missense mutation (P132L) was found. Functional analysis demonstrated that the P132L mutant had low residual activity.

Conclusions: In combination with data presented in literature, we conclude that type I BOCD is caused by a complete inactivation of the PTHR1, whereas low levels of residual activity due to a near complete inactivation of the PTHR1 result in the relatively milder presentation of type II BOCD.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Cells, Cultured
  • Chlorocebus aethiops
  • Diagnosis
  • Humans
  • Infant, Newborn
  • Models, Biological
  • Molecular Sequence Data
  • Mutation*
  • Osteochondrodysplasias / diagnosis
  • Osteochondrodysplasias / genetics*
  • Parathyroid Hormone / genetics*
  • Receptor, Parathyroid Hormone, Type 1 / genetics*
  • Transfection


  • PTH protein, human
  • Parathyroid Hormone
  • Receptor, Parathyroid Hormone, Type 1