Multiple osteochondromas: Mutation update and description of the Multiple Osteochondromas Mutation Database (MOdb)

Ivy Jennes, Elena Pedrini, Monia Zuntini, Marina Mordenti, Sahila Balkassmi, Carla G. Asteggiano, Brett Casey, Bert Bakker, Luca Sangiorgi, Wim Wuyts

Research output: Contribution to journalArticlepeer-review

Abstract

Multiple osteochondromas (MO) is an autosomal dominant skeletal disease characterized by the formation of multiple cartilage-capped bone tumors growing outward from the metaphyses of long tubular bones. MO is genetically heterogeneous, and is associated with mutations in Exostosin-1 (EXT1) or Exostosin-2 (EXT2), both tumor-suppressor genes of the EXT gene family. All members of this multigene family encode glycosyltransferases involved in the adhesion and/or polymerization of heparin sulfate (HS) chains at HS proteoglycans (HSPGs). HSPGs have been shown to play a role in the diffusion of Ihh, thereby regulating chondrocyte proliferation and differentiation. EXT1 is located at 8q24.11-q24.13, and comprises 11 exons, whereas the 16 exon EXT2 is located at 11p12-p11. To date, an EXT1 or EXT2 mutation is detected in 70-95% of affected individuals. EXT1 mutations are detected in ±65% of cases, versus ±35% EXT2 mutations in MO patient cohorts. Inactivating mutations (nonsense, frame shift, and splice-site mutations) represent the majority of MO causing mutations (75-80%). In this article, the clinical aspects and molecular genetics of EXT1 and EXT2 are reviewed together with 895 variants in MO patients. An overview of the reported variants is provided by the online Multiple Osteochondromas Mutation Database (http://medgen.ua.ac.be/LOVD).

Original languageEnglish
Pages (from-to)1620-1627
Number of pages8
JournalHuman Mutation
Volume30
Issue number12
DOIs
Publication statusPublished - Dec 2009

Keywords

  • Exostoses
  • EXT1
  • EXT2
  • MO
  • Multiple osteochondromas

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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