P106. Congenital hypertelorism and osteopenia: A novel autosomal recessive disease

A novel autosomal recessive syndrome with congenital heart, blood, bone and craniofacial defects was delineated by homozygosity mapping in two inbred families. Independent disease-causing mutations were found in one of the Iroquois (IRX) transcription factors. In light of these findings, we re-evaluated its role during embryogenesis in Xenopus. By Morpholino knock-down, this Irx gene was found to be necessary for migration of neural crest cells (NCC) in the first branchial arch, differentiation of the hematopoietic lineage and cardiogenesis. Ongoing investigations using Chip-Seq and a two-hybrid screen will attempt to uncover the exact mechanism by which this particular Iroquois gene controls NCC migration and also leads to both osteoporosis and anemia in humans.