Novel MSX1 variants identified in families with nonsyndromic oligodontia  

作　　者：Jinglei Zheng Miao Yu Haochen Liu Tao Cai Hailan Feng Yang Liu Dong Han 

机构地区：[1]Department of Prosthodontics,Peking University School and Hospital of Stomatology&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology,Beijing,China [2]National Institute of Dental and Craniofacial Research,NIH,Bethesda,MD,USA

出　　处：《International Journal of Oral Science》2021年第1期42-51,共10页国际口腔科学杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China(81970902,81771054,and 81600846).

摘　　要：The goal of this study was to identify MSX1 gene variants in multiple Chinese families with nonsyndromic oligodontia and analyse the functional influence of these variants.Whole-exome sequencing(WES)and Sanger sequencing were performed to identify the causal gene variants in five families with nonsyndromic oligodontia,and a series of bioinformatics databases were used for variant confirmation and functional prediction.Phenotypic characterization of the members of these families was described,and an in vitro analysis was performed for functional evaluation.Five novel MSX1 heterozygous variants were identified:three missense variants[c.662A>C(p.Q221P),c.670C>T(p.R224C),and c.809C>T(p.S270L)],one nonsense variant[c.364G>T(p.G122*)],and one frameshift variant[c.277delG(p.A93Rfs*67)].Preliminary in vitro studies demonstrated that the subcellular localization of MSX1 was abnormal with the p.Q221P,p.R224C,p.G122*,and p.A93Rfs*67 variants compared to the wild type.Three variants(p.Q221P,p.G122*,and p.A93Rfs*67)were classified as pathogenic or likely pathogenic,while p.S270L and p.R224C were of uncertain significance in the current data.Moreover,we summarized and analysed the MSX1-related tooth agenesis positions and found that the type and variant locus were not related to the severity of tooth loss.Our results expand the variant spectrum of nonsyndromic oligodontia and provide valuable information for genetic counselling.

关 键 词：MSX1 VARIANTS LIKELY 

分 类 号：R783.6[医药卫生—口腔医学]