Determination of the chromosomal location and genomic structure of the Hedgehog-Interacting Protein gene, and analysis of its role in Holoprosencephaly

Hedgehog-Interacting Protein (HIP) is a novel component of the Sonic Hedgehog (SHH) signaling pathway. Recently, defects in this pathway have been shown to cause holoprosencephaly (HPE), which is the most common birth defect of the brain and face in humans. In animal models knockout mice with homozygous null mutations for Shh displayed abnormalities consistent with HPE. Hip has been shown to function as a co-receptor and attenuate Hedgehog signaling by cell-surface binding of the Hedgehog protein and is hypothesized to act as part of a negative regulatory feedback loop. Although Hip is an important factor in the Shh signaling pathway, its potential role in HPE had not been examined in humans. Here, we report the complete gene structure of the human HIP gene and present its mutational analysis in HPE patients. No mutations were found either in the entire coding region or 1 kb upstream of the transcriptional start site (representing the putative promotor) suggesting this gene may not be involved in HPE pathogenesis.