ITPR1 Mutation Contributes to Hemifacial Microsomia Spectrum

Zhixu Liu; Hao Sun; Jiewen Dai; Xiaochen Xue; Jian Sun; Xudong Wang

doi:10.3389/fgene.2021.616329

ITPR1 Mutation Contributes to Hemifacial Microsomia Spectrum

Front Genet. 2021 Mar 4:12:616329. doi: 10.3389/fgene.2021.616329. eCollection 2021.

Authors

Zhixu Liu^{1

2

3}, Hao Sun^{1

3}, Jiewen Dai^{1

3}, Xiaochen Xue^{1

3}, Jian Sun^{1

3}, Xudong Wang^{1

3}

Affiliations

¹ Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration, Ministry of Education, Tongji University, Shanghai, China.
³ National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.

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.

Keywords: DLX5; DLX6; ITPR1; PLCB4; hemifacial microsomia; zebrafish.