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Genet."],"abstract":"<jats: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<jats:italic>ITPR1<\/jats:italic>. ITPR1 is a calcium ion channel. By studying<jats:italic>ITPR1<\/jats:italic>\u2019s expression pattern, we found that ITPR1 participated in craniofacial development, especially the organs that corresponded to the phenotype of HM. In zebrafish,<jats:italic>itpr1b<\/jats:italic>, which is homologous to human<jats:italic>ITPR1<\/jats:italic>, is closely related to craniofacial bone formation. The knocking down of<jats:italic>itpr1b<\/jats:italic>in zebrafish could lead to a remarkable decrease in craniofacial skeleton formation. qRT-PCR suggested that knockdown of<jats:italic>itpr1b<\/jats:italic>could increase the expression of<jats:italic>plcb4<\/jats:italic>while decreasing the mRNA level of Dlx5\/6. Our findings highlighted ITPR1\u2019s role in craniofacial formation for the first time and suggested that<jats:italic>ITPR1<\/jats:italic>mutation contributes to human HM.<\/jats:p>","DOI":"10.3389\/fgene.2021.616329","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T17:05:27Z","timestamp":1614877527000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["ITPR1 Mutation Contributes to Hemifacial Microsomia Spectrum"],"prefix":"10.3389","volume":"12","author":[{"given":"Zhixu","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiewen","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1136\/jmedgenet-2018-105358","article-title":"Use of zebrafish models to investigate rare human disease.","volume":"55","author":"Adamson","year":"2018","journal-title":"J. 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