A Mechanism for Gene-Environment Interaction in the Etiology of Congenital Scoliosis

作者：Sparrow Duncan B^*; Chapman Gavin; Smith Allanceson J; Mattar Muhammad Z; Major Joelene A; O' Reilly Victoria C; Saga Yumiko; Zackai Elaine H; Dormans John P; Alman Benjamin A; McGregor Lesley; Kageyama Ryoichiro; Kusumi Kenro; Dunwoodie Sally L

来源：Cell, 2012, 149(2): 295-306.

DOI：10.1016/j.cell.2012.02.054

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.

• 出版日期2012-4-13
• 单位河北医科大学