Using samples from a population-based birth defects registry in California, we performed a mutational analysis of the known HPE genes Sonic Hedgehog (SHH), ZIC2, and SIX3, in addition to two HPE candidate genes, TG-interacting factor (TGIF), and Patched (PTC), on a group of sporadic HPE patients.
Mutational analysis has identified four different mutations in the homeodomain of SIX3 that are predicted to interfere with transcriptional activation and are associated with HPE.
Mutational analysis has identified four different mutations in the homeodomain of SIX3 that are predicted to interfere with transcriptional activation and are associated with HPE.
These YACs narrow the HPE2 critical region to less than 1 Mb and are now being further analyzed to identify the gene causing holoprosencephaly on chromosome 2.