Pathogenic Variants in SHROOM3 Associated with Hemifacial Microsomia

Abstract Purpose: Hemifacial microsomia (HFM) is a rare congenital disorder that affects facial symmetry, ear development, and other congenital features. However, known causal genes only account for approximately 3% of patients, indicating the need to discover more pathogenic genes. Methods: We performed target capture sequencing on SHROOM3 in 320 Chinese HFM patients and evaluated the expression pattern of SHROOM3 and the consequences of deleterious mutations. Results: Our study identified 9 deleterious mutations in SHROOM3 in 320 Chinese HFM patients. These mutations were predicted to significantly impact SHROOM3 function. Furthermore, the gene expression pattern of SHROOM3 in pharyngeal arches and the presence of facial abnormalities in gene-edited mice suggest important roles of SHROOM3 in facial development. Conclusion: Our findings suggest that SHROOM3 i s a likely pathogenic gene for HFM.