A Mutation in VWA1, Encoding von Willebrand Factor A Domain-Containing Protein 1, Is Associated With Hemifacial Microsomia

• DOI: 10.3389/fcell.2020.571004
• Publication Date: 2020-09-09T05:18:13Z
• Authors: Yibei Wang; Lu Ping; Xiaodong Luan; Yushan Chen; Xinmiao Fan; Lianyan Li; Yaping Liu; Pu Wang; Shuyang Zhang; Bo Zhang; Xiaowei Chen
• Keywords: Hemifacial microsomia

Background Hemifacial microsomia (HFM) is a type of rare congenital syndrome caused by developmental disorders the first and second pharyngeal arches that occurs in one out ~5,600 live births. There are significant gaps our knowledge pathogenic genes underlying this syndrome. Methods Whole exome sequencing (WES) was performed on five patients, asymptomatic carrier, two marry-in members five-generation pedigree. Structure WARP (product VWA1) predicted using Phyre2 web portal. In situ hybridization vwa1-knockdown/knockout studies zebrafish morpholino CRISPR/Cas9 techniques were performed. Cartilage staining immunofluorescence carried out. Results Through WES set filtration, we identified c.G905A:p.R302Q point mutation novel candidate gene, VWA1. The portal alterations secondary tertiary structures WARP, indicating changes its function as well. Predictions protein-to-protein interactions pathways related to craniofacial development revealed possible with four proteins FGF pathway. Knockdown/knockout deformities cartilage. A decrease proliferation cranial neural crest cells (CNCCs) alteration structure chondrocytes observed morphants Conclusion Our data suggest VWA1 functionally linked HFM through suppression CNCC disruption organization chondrocytes.