Abnormal vertebral segmentation and the notch signaling pathway in man.

Journal Article (Journal Article;Review)

Abnormal vertebral segmentation (AVS) in man is a relatively common congenital malformation but cannot be subjected to the scientific analysis that is applied in animal models. Nevertheless, some spectacular advances in the cell biology and molecular genetics of somitogenesis in animal models have proved to be directly relevant to human disease. Some advances in our understanding have come through DNA linkage analysis in families demonstrating a clustering of AVS cases, as well as adopting a candidate gene approach. Only rarely do AVS phenotypes follow clear Mendelian inheritance, but three genes-DLL3, MESP2, and LNFG-have now been identified for spondylocostal dysostosis (SCD). SCD is characterized by extensive hemivertebrae, trunkal shortening, and abnormally aligned ribs with points of fusion. In familial cases clearly following a Mendelian pattern, autosomal recessive inheritance is more common than autosomal dominant and the genes identified are functional within the Notch signaling pathway. Other genes within the pathway cause diverse phenotypes such as Alagille syndrome (AGS) and CADASIL, conditions that may have their origin in defective vasculogenesis. Here, we deal mainly with SCD and AGS, and present a new classification system for AVS phenotypes, for which, hitherto, the terminology has been inconsistent and confusing.

Full Text

Duke Authors

Cited Authors

  • Turnpenny, PD; Alman, B; Cornier, AS; Giampietro, PF; Offiah, A; Tassy, O; Pourquié, O; Kusumi, K; Dunwoodie, S

Published Date

  • June 2007

Published In

Volume / Issue

  • 236 / 6

Start / End Page

  • 1456 - 1474

PubMed ID

  • 17497699

International Standard Serial Number (ISSN)

  • 1058-8388

Digital Object Identifier (DOI)

  • 10.1002/dvdy.21182


  • eng

Conference Location

  • United States