目的:研究MSX1基因外显子区rs13127820(M146L)、rs62636562(A274V)位点多态性与非综合征性唇腭裂(non-syn-dromic cleft lip with or without cleft palate,NSCL/P)的关系。方法:通过聚合酶链反应-限制性片段长度多态性方法,检测243例...目的:研究MSX1基因外显子区rs13127820(M146L)、rs62636562(A274V)位点多态性与非综合征性唇腭裂(non-syn-dromic cleft lip with or without cleft palate,NSCL/P)的关系。方法:通过聚合酶链反应-限制性片段长度多态性方法,检测243例非综合征性唇腭裂(NSCL/P)患者和292例正常对照者全血标本中MSX1基因rs13127820(M146L)、rs62636562(A274V)位点的多态性。结果:MSX1基因位点rs13127820(M146L)、rs62636562(A274V)基因型频率分布符合Hardy-Weinberg平衡;MSX1基因位点rs13127820(M146L)、rs62636562(A274V)等位基因频率分布在NSCL/P组与对照组之间差异有统计学意义(P<0.05)。结论:结果显示MSX1基因位点多态性与NSCL/P的发生有关。展开更多
目的研究同源异型盒基因1(muscle segment homeobox1,MSX1)A274V多态性与非综合征性唇腭裂(non-syndromic cleft lip with or without cleft palate,NSCL/P)的关系。方法利用聚合酶链反应-限制性片段长度多态性方法,在162例非综合性唇...目的研究同源异型盒基因1(muscle segment homeobox1,MSX1)A274V多态性与非综合征性唇腭裂(non-syndromic cleft lip with or without cleft palate,NSCL/P)的关系。方法利用聚合酶链反应-限制性片段长度多态性方法,在162例非综合性唇腭裂患者和195例正常对照中,对MSX1基因A274V单核苷酸多态性进行检测。分析基因型发布频率是否符合Hardy-Weinberg平衡定律。应用UNPHASED软件包分析多态性位点与非综合性唇腭裂的相关性。结果 MSX1 A274V多态性基因型频率分布符合Hardy-Weinberg平衡定律。MSX1 A274V等位基因分布在NSCL/P组与对照组之间有显著性差异(P<0.05)。在NSCL/P组中T等位基因的频率明显高于对照组。结论 MSX1 A274V多态性位点与中国人群非综合性唇腭裂形成相关联。展开更多
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 sequenc...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.展开更多
文摘目的:研究MSX1基因外显子区rs13127820(M146L)、rs62636562(A274V)位点多态性与非综合征性唇腭裂(non-syn-dromic cleft lip with or without cleft palate,NSCL/P)的关系。方法:通过聚合酶链反应-限制性片段长度多态性方法,检测243例非综合征性唇腭裂(NSCL/P)患者和292例正常对照者全血标本中MSX1基因rs13127820(M146L)、rs62636562(A274V)位点的多态性。结果:MSX1基因位点rs13127820(M146L)、rs62636562(A274V)基因型频率分布符合Hardy-Weinberg平衡;MSX1基因位点rs13127820(M146L)、rs62636562(A274V)等位基因频率分布在NSCL/P组与对照组之间差异有统计学意义(P<0.05)。结论:结果显示MSX1基因位点多态性与NSCL/P的发生有关。
文摘目的研究同源异型盒基因1(muscle segment homeobox1,MSX1)A274V多态性与非综合征性唇腭裂(non-syndromic cleft lip with or without cleft palate,NSCL/P)的关系。方法利用聚合酶链反应-限制性片段长度多态性方法,在162例非综合性唇腭裂患者和195例正常对照中,对MSX1基因A274V单核苷酸多态性进行检测。分析基因型发布频率是否符合Hardy-Weinberg平衡定律。应用UNPHASED软件包分析多态性位点与非综合性唇腭裂的相关性。结果 MSX1 A274V多态性基因型频率分布符合Hardy-Weinberg平衡定律。MSX1 A274V等位基因分布在NSCL/P组与对照组之间有显著性差异(P<0.05)。在NSCL/P组中T等位基因的频率明显高于对照组。结论 MSX1 A274V多态性位点与中国人群非综合性唇腭裂形成相关联。
基金supported by the National Natural Science Foundation of China(81970902,81771054,and 81600846).
文摘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.
