Pathogenic variants in shroom3 associated with hemifacial microsomia

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. Access through your institution Buy or subscribe This is a preview of subscription

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CRANIOFACIAL MICROSOMIA Article Open access 03 August 2021 _FOXI3_ PATHOGENIC VARIANTS CAUSE ONE FORM OF CRANIOFACIAL MICROSOMIA Article Open access 11 April 2023 _MITF_ VARIANTS CAUSE

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the patients and their guardians for their participation in this research. This work was supported by the National Natural Science Foundation of China (81701930 to B.Q.W.). AUTHOR

INFORMATION Author notes * These authors contributed equally: Qin Li, Bing-Hua Zhang. AUTHORS AND AFFILIATIONS * Department of Stomatology, Eye&ENT Hospital, Fudan University, Shanghai,

200031, China Qin Li, Xiang Zuo & Weiwei Zhang * Shanghai Xuhui District Dental Center, Shanghai, 200032, China Bing-Hua Zhang * Plastic Surgery Hospital, Chinese Academy of Medical

Sciences and Peking Union Medical College, Beijing, 100144, China Qi Chen, Peng Lu & Bingqing Wang * Department of facial plastic and reconstructive surgery, Eye&ENT Hospital, Fudan

University, Shanghai, 200031, China Yaoyao Fu Authors * Qin Li View author publications You can also search for this author inPubMed Google Scholar * Bing-Hua Zhang View author publications

You can also search for this author inPubMed Google Scholar * Qi Chen View author publications You can also search for this author inPubMed Google Scholar * Yaoyao Fu View author

publications You can also search for this author inPubMed Google Scholar * Xiang Zuo View author publications You can also search for this author inPubMed Google Scholar * Peng Lu View

author publications You can also search for this author inPubMed Google Scholar * Weiwei Zhang View author publications You can also search for this author inPubMed Google Scholar * Bingqing

Wang View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS Conceptualization: B.W., W.Z.; Sample collection: W.Z., B.-H.Z., P.L.; Experiments:

Q.L., B.-H.Z., Q.C.; Data analysis: Q.L., B.-H.Z., X.Z.; Writing-original draft: B.W., Q.L., W.Z.; Writing-reviewing and editing: W.Z., B.W. CORRESPONDING AUTHORS Correspondence to Weiwei

Zhang or Bingqing Wang. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflicts of interest. ETHICS All human studies were reviewed and approved by the Ethics Committee of

the Eye & ENT Hospital of Fudan University. An informed consent form was signed by all individuals, and explicit written consent was provided for publication of clinical images.

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_et al._ Pathogenic variants in _SHROOM3_ associated with hemifacial microsomia. _J Hum Genet_ 70, 189–194 (2025). https://doi.org/10.1038/s10038-025-01317-1 Download citation * Received: 15

May 2024 * Revised: 14 December 2024 * Accepted: 15 January 2025 * Published: 28 January 2025 * Issue Date: April 2025 * DOI: https://doi.org/10.1038/s10038-025-01317-1 SHARE THIS ARTICLE

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