ITPR1 Mutation Contributes to Hemifacial Microsomia Spectrum

Abstract

Hemifacial microsomia (HM) is a craniofacial congenital defect involving the first and second branchial arch, mainly characterized by ocular, ear, maxilla-zygoma complex, mandible, and facial nerve malformation. HM follows autosomal dominant inheritance. Whole-exome sequencing of a family revealed a missense mutation in a highly conserved domain ofITPR1. ITPR1 is a calcium ion channel. By studyingITPR1’s expression pattern, we found that ITPR1 participated in craniofacial development, especially the organs that corresponded to the phenotype of HM. In zebrafish,itpr1b, which is homologous to humanITPR1, is closely related to craniofacial bone formation. The knocking down ofitpr1bin zebrafish could lead to a remarkable decrease in craniofacial skeleton formation. qRT-PCR suggested that knockdown ofitpr1bcould increase the expression ofplcb4while decreasing the mRNA level of Dlx5/6. Our findings highlighted ITPR1’s role in craniofacial formation for the first time and suggested thatITPR1mutation contributes to human HM.