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 of ITPR1 . ITPR1 is a calcium ion channel. By studying ITPR1 ’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 human ITPR1 , is closely related to craniofacial bone formation. The knocking down of itpr1b in zebrafish could lead to a remarkable decrease in craniofacial skeleton formation. qRT-PCR suggested that knockdown of itpr1b could increase the expression of plcb4 while decreasing the mRNA level of Dlx5/6. Our findings highlighted ITPR1’s role in craniofacial formation for the first time and suggested that ITPR1 mutation contributes to human HM.