AUTHOR=Liu Zhixu , Sun Hao , Dai Jiewen , Xue Xiaochen , Sun Jian , Wang Xudong 

TITLE=ITPR1 Mutation Contributes to Hemifacial Microsomia Spectrum

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.616329

DOI=10.3389/fgene.2021.616329

ISSN=1664-8021

ABSTRACT=<p>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 <italic>ITPR1</italic>. ITPR1 is a calcium ion channel. By studying <italic>ITPR1</italic>’s expression pattern, we found that ITPR1 participated in craniofacial development, especially the organs that corresponded to the phenotype of HM. In zebrafish, <italic>itpr1b</italic>, which is homologous to human <italic>ITPR1</italic>, is closely related to craniofacial bone formation. The knocking down of <italic>itpr1b</italic> in zebrafish could lead to a remarkable decrease in craniofacial skeleton formation. qRT-PCR suggested that knockdown of <italic>itpr1b</italic> could increase the expression of <italic>plcb4</italic> while decreasing the mRNA level of Dlx5/6. Our findings highlighted ITPR1’s role in craniofacial formation for the first time and suggested that <italic>ITPR1</italic> mutation contributes to human HM.</p>