Missense substitutions in the GAS1 protein present in holoprosencephaly patients reduce the affinity for its ligand, SHH.

ABSTRACT: Holprosencephaly (HPE) is the most common disorder of the developing forebrain in humans, and is characterized by varying degrees of abnormal union of the cerebral hemispheres. These defects are typically co-associated with midline craniofacial anomalies. The combination of forebrain and craniofacial defects that comprise HPE can present along a broad and variable phenotypic spectrum. Both the SHH and NODAL signaling pathways play important roles in the pathogenesis of this disorder. Disruption of these pathways by chromosomal rearrangements, mutations in pathway-related genes and/or biochemical alterations are proposed to contribute to HPE in a large number of patients. Additional factors that are not yet fully delineated are also very likely to be involved in the pathogenesis and phenoty

SUBMITTER: Pineda-Alvarez DE 

PROVIDER: S-EPMC3695622 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature