Related Experiment Video
Updated: May 30, 2025
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Pathogenic variants in SHROOM3 associated with hemifacial microsomia
Qin Li1, Bing-Hua Zhang2, Qi Chen3
1Department of Stomatology, Eye&ENT Hospital, Fudan University, Shanghai, 200031, China.
Abstract:
Hemifacial microsomia (HFM) is a rare congenital disorder that affects facial symmetry, ear development, and other congenital anomalies. However, known causal genes account for only approximately 6% of patients, indicating the need to discover more pathogenic genes. Association tests demonstrated an association between common variants in SHROOM3 and HFM (P = 1.02E-4 for the lead SNP), while gene burden analysis revealed a significant enrichment of rare variants in HFM patients compared to healthy controls (P = 2.78E-5). We then evaluated the expression patterns of SHROOM3 and the consequences of its deleterious variants. Our study identified 7 deleterious variants in SHROOM3 among the 320 Chinese HFM patients and 2 deleterious variants in two HFM trios, respectively, suggesting a model of dominant inheritance with incomplete penetrance. These variants were predicted to significantly impact SHROOM3 function. Furthermore, the gene expression pattern of SHROOM3 in the pharyngeal arches and the presence of facial abnormalities in gene-edited mice suggest that SHROOM3 plays important roles in facial development. Our findings suggest that SHROOM3 is a likely pathogenic gene for HFM.
Insights
SHROOM3 is identified as a likely pathogenic gene for Hemifacial Microsomia (HFM), a rare congenital disorder. This discovery offers new insights into HFM
Area of Science:
- Genetics
- Developmental Biology
- Medical Research
Background:
- Hemifacial Microsomia (HFM) is a rare congenital disorder impacting facial symmetry and development.
- Known genetic causes explain only a small fraction of HFM cases, necessitating further gene discovery.
Purpose of the Study:
- To investigate the role of the SHROOM3 gene in the etiology of Hemifacial Microsomia.
- To identify novel pathogenic variants in SHROOM3 associated with HFM.
Main Methods:
- Genome-wide association studies and gene burden analysis were performed on HFM patients.
- Deleterious SHROOM3 variants were identified and functionally evaluated.
- SHROOM3 expression patterns and effects of gene editing in mice were examined.
Main Results:
- Common variants in SHROOM3 showed association with HFM, and rare variants were significantly enriched in HFM patients.
- Seven deleterious SHROOM3 variants were found in Chinese HFM patients, suggesting dominant inheritance with incomplete penetrance.
- SHROOM3 expression in pharyngeal arches and facial abnormalities in gene-edited mice support its role in facial development.
Conclusions:
- SHROOM3 is implicated as a likely pathogenic gene contributing to Hemifacial Microsomia.
- The findings expand the genetic understanding of HFM and highlight SHROOM3 as a potential therapeutic target.
More Related Videos
09:37Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
08:22A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
Published on: December 1, 2017
