首页|Rare loss-of-function variants in FLNB cause non-syndromic orofacial clefts

Rare loss-of-function variants in FLNB cause non-syndromic orofacial clefts

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Orofacial clefts(OFCs)are the most common congenital craniofacial disorders,of which the etiology is closely related to rare coding variants.Filamin B(FLNB)is an actin-binding protein implicated in bone formation.FLNB mutations have been identified in several types of syndromic OFCs and previous studies suggest a role of FLNB in the onset of non-syndromic OFCs(NSOFCs).Here,we report two rare heterozygous variants(p.P441T and p.G565R)in FLNB in two unrelated hereditary families with NSOFCs.Bioinformatics analysis suggests that both variants may disrupt the function of FLNB.In mammalian cells,p.P441T and p.G565R variants are less potent to induce cell stretches than wild type FLNB,suggesting that they are loss-of-function mutations.Immunohistochemistry analysis demon-strates that FLNB is abundantly expressed during palatal development.Importantly,Flnb-/-embryos display cleft palates and previously defined skeletal defects.Taken together,our findings reveal that FLNB is required for development of palates in mice and FLNB is a bona fide causal gene for NSOFCs in humans.

Orofacial cleftsFLNBLoss-of-function mutationCleft palateFilamin BActin filamentKnockout mouse

Wenbin Huang、Shiying Zhang、Jiuxiang Lin、Yi Ding、Nan Jiang、Jieni Zhang、Huaxiang Zhao、Feng Chen

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Department of Orthodontics,Peking University School and Hospital of Stomatology,Beijing,100081,China

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research,College of Stomatology,Xi'an Jiaotong University,Xi'an,Shaanxi,710004,China

Guangdong Provincial High-level Clinical Key Specialty,Guangdong Province Engineering Research Center of Oral Disease Diagnosis and Treatment,Department of Orthodontics,Stomatological Center,Peking University Shenzhen Hospital,Shenzhen Peking University-T

Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Xian Jiaotong University,Xi'an,Shaanxi,710049,China

National Center for Stomatology,National Clinical Research Center for Oral Diseases,National Engineering Laboratory for Digital and Material Technology of Stomatology,Beijing Key Laboratory for Digital Stomatology,Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health,NMPA Key Laboratory for Dental Materials,Beijing,100101,China

Central Laboratory,Peking University School and Hospital of Stomatology,Beijing,100081,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaFundamental Research Funds for the Central UniversitiesNatural Science Foundation of Beijing MunicipalityXi'anScience and TechnologyFundamental Research Funds for the Central Universities

81870747821709168190098482001030PKU2022XGK001718218420YXYJ0010[1]xzy012020110

2024

10.1016/j.jgg.2023.03.012

遗传学报
中国遗传学会 中国科学院遗传与发育生物学研究所

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CSTPCD
影响因子：0.821
ISSN：1673-8527
年,卷(期)：2024.51(2)
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