Copy-number variations involving the IHH locus are associated with syndactyly and craniosynostosis

Am J Hum Genet. 2011 Jan 7;88(1):70-5. doi: 10.1016/j.ajhg.2010.11.006. Epub 2010 Dec 17.

Abstract

Indian hedgehog (IHH) is a secreted signaling molecule of the hedgehog family known to play important roles in the regulation of chondrocyte differentiation, cortical bone formation, and the development of joints. Here, we describe that copy-number variations of the IHH locus involving conserved noncoding elements (CNEs) are associated with syndactyly and craniosynostosis. These CNEs are able to drive reporter gene expression in a pattern highly similar to wild-type Ihh expression. We postulate that the observed duplications lead to a misexpression and/or overexpression of IHH and by this affect the complex regulatory signaling network during digit and skull development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conserved Sequence / genetics
  • Craniosynostoses / genetics*
  • DNA Copy Number Variations*
  • Female
  • Fingers / growth & development
  • Gene Duplication*
  • Gene Expression Regulation, Developmental / genetics
  • Genetic Loci*
  • Hedgehog Proteins / genetics*
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Mutation
  • Skull / growth & development
  • Syndactyly / genetics*

Substances

  • Hedgehog Proteins
  • IHH protein, human
  • ihh protein, mouse