Localization of the gene causing autosomal dominant osteopetrosis type I to chromosome 11q12-13

J Bone Miner Res. 2002 Jun;17(6):1111-7. doi: 10.1359/jbmr.2002.17.6.1111.

Abstract

The osteopetroses are a heterogeneous group of genetic conditions characterized by increased bone density due to impaired bone resorption by osteoclasts. Within the autosomal dominant form of osteopetrosis, the radiological type I (ADOI) is characterized by a generalized osteosclerosis, most pronounced at the cranial vault. The patients are often asymptomatic but some suffer from pain and hearing loss. ADOI is the only type of osteopetrosis not associated with an increased fracture rate. Linkage analysis in two families with ADOI from Danish origin enabled us to assign the disease-causing gene to chromosome 11q12-13. A summated maximum lod score of +6.54 was obtained with marker D11S1889 and key recombinants allowed delineation of a candidate region of 6.6 cM between markers D11S1765 and D11S4113. Previously, genes causing other conditions with abnormal bone density have been identified from this chromosomal region. The TCIRG1 gene was shown to underly autosomal recessive osteopetrosis (ARO), and, recently, mutations in the LRP5 gene were found both in the osteoporosis-pseudoglioma syndrome and the high bone mass trait. Because both genes map within the candidate region for ADOI, it can not be excluded that ADOI is caused by mutations in either the TCIRG1 or the LRP5 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 11*
  • Female
  • Genes, Dominant*
  • Humans
  • LDL-Receptor Related Proteins
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Male
  • Mutation
  • Osteopetrosis / diagnostic imaging
  • Osteopetrosis / genetics*
  • Pedigree
  • Radiography
  • Receptors, LDL / genetics*

Substances

  • LDL-Receptor Related Proteins
  • LRP5 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Receptors, LDL