This study also identified genes not previously implicated in human HPE, but for which mouse studies suggested a potential role, including COL2A1, and NDST1. COL2A1 encodes a collagen isoform and NDST1 encodes a heparan sulfate-modifying enzyme; these factors act extracellularly to regulate HH signaling in forebrain and craniofacial development (Grobe et al., 2005; Leung et al., 2010). This evidence concerns the gene COL2A1 and holoprosencephaly.