Cdon mutation and fetal ethanol exposure synergize to produce midline signaling defects and holoprosencephaly spectrum disorders in mice.

ABSTRACT: Holoprosencephaly (HPE) is a remarkably common congenital anomaly characterized by failure to define the midline of the forebrain and midface. HPE is associated with heterozygous mutations in Sonic hedgehog (SHH) pathway components, but clinical presentation is extremely variable and many mutation carriers are unaffected. It has been proposed that these observations are best explained by a multiple-hit model, in which the penetrance and expressivity of an HPE mutation is enhanced by a second mutation or the presence of cooperating, but otherwise silent, modifier genes. Non-genetic risk factors are also implicated in HPE, and gene-environment interactions may provide an alternative multiple-hit model to purely genetic multiple-hit models; however, there is little evidence for this contentio

SUBMITTER: Hong M 

PROVIDER: S-EPMC3469434 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature