A mechanism for gene-environment interaction in the etiology of congenital scoliosis.

Journal Article (Journal Article)

Congenital scoliosis, a lateral curvature of the spine caused by vertebral defects, occurs in approximately 1 in 1,000 live births. Here we demonstrate that haploinsufficiency of Notch signaling pathway genes in humans can cause this congenital abnormality. We also show that in a mouse model, the combination of this genetic risk factor with an environmental condition (short-term gestational hypoxia) significantly increases the penetrance and severity of vertebral defects. We demonstrate that hypoxia disrupts FGF signaling, leading to a temporary failure of embryonic somitogenesis. Our results potentially provide a mechanism for the genesis of a host of common sporadic congenital abnormalities through gene-environment interaction.

Full Text

Duke Authors

Cited Authors

  • Sparrow, DB; Chapman, G; Smith, AJ; Mattar, MZ; Major, JA; O'Reilly, VC; Saga, Y; Zackai, EH; Dormans, JP; Alman, BA; McGregor, L; Kageyama, R; Kusumi, K; Dunwoodie, SL

Published Date

  • April 13, 2012

Published In

Volume / Issue

  • 149 / 2

Start / End Page

  • 295 - 306

PubMed ID

  • 22484060

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2012.02.054


  • eng

Conference Location

  • United States