ITPR1 Mutation Contributes to Hemifacial Microsomia Spectrum

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

doi:10.3389/fgene.2021.616329

Frontiers in Genetics (Mar 2021)

ITPR1 Mutation Contributes to Hemifacial Microsomia Spectrum

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

Affiliations

Zhixu Liu: Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Zhixu Liu: Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration, Ministry of Education, Tongji University, Shanghai, China
Zhixu Liu: National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
Hao Sun: Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Hao Sun: National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
Jiewen Dai: Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Jiewen Dai: National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
Xiaochen Xue: Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Xiaochen Xue: National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
Jian Sun: Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Jian Sun: National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China
Xudong Wang: Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Xudong Wang: National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China

DOI: https://doi.org/10.3389/fgene.2021.616329
Journal volume & issue: Vol. 12

Abstract

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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.

Published in Frontiers in Genetics

ISSN: 1664-8021 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General): Genetics
Website: http://journal.frontiersin.org/journal/genetics

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