一个Pelger-Huёt异常家系的LBR基因突变分析  

Analysis of LBR gene mutation in a pedigree affected with Pelger-Huёt anomaly

作　　者：罗晓成 徐琴 黄凌[2] 杨楠楠 李媛媛[2] 曾强武[4] 安邦权[2] 黄盛文[2] Luo Xiaocheng;Xu Qin;Huang Ling;Yang Nannan;Li Yuanyuan;Zeng Qiangwu;An Bangquan;Huang Shengwen(Department of Laboratory Medicine,People's Hospital of Mashan County,Guangxi 530699,China;Department of Laboratory Medicine,Guizhou Provincial People's Hospital,Guiyang,Guizhou 550002,China;Department of Oncology,Tongren People's Hos pital,Guizhou 554300,China;Department of Laboratory Medicine,the First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine,Guiyang,Guizhou 550001,China)

机构地区：[1]马山县人民医院检验科,广西530699 [2]贵州省人民医院检验科,贵阳550002 [3]铜仁市人民医院肿瘤科,贵州554300 [4]贵阳中医学院第一附属医院检验科550001

出　　处：《中华医学遗传学杂志》2019年第9期905-909,共5页Chinese Journal of Medical Genetics

基　　金：贵州省科技计划项目(黔科合平台人才[2016]5670号);贵阳市科技创新平台计划项目([20161001]35号).

摘　　要：目的 确定1个白细胞Pelger-Huёt异常(Pelger-Huёt anomaly,PHA)家系LBR基因的突变类型并分析其临床特征.方法 提取该家系成员及正常对照的基因组DNA,针对LBR基因的14个外显子分别设计引物并进行PCR扩增.先将家系先证者和1名正常者的扩增产物进行Sanger测序,将测序结果与GenBank中所提供的LBR基因参考序列进行比对,筛选出突变位点.对家系其他成员及100名正常对照者进行相应突变位点验证.应用PolyPhen-2和SIFT软件预测突变位点对蛋白功能的影响,并用SWISS-MODEL软件对蛋白结构进行模拟分析.结果 PHA家系3例患者的LBR基因第8外显子上携带有c.893G>A突变,导致第298位氨基酸由甘氨酸替换为谷氨酸(p.Gly 298 Glu).该突变位点在家系其他成员和100名正常对照未发现.该突变的蛋白功能预测均为有害,分子模拟显示突变后LBR蛋白的三维构象发生改变.结论 LBR基因c.893 G>A(p.Gly 298 Glu)突变导致该家系白细胞Pelger-Huёt异常.该突变在国际上未见报道,丰富了LBR基因突变谱.Objective To detect mutation of LBR gene in a pedigree affected with Pelger-Huёt anomaly(PHA)and to explore its clinical characteristics.Methods Genomic DNA was extracted from the pedigree and healthy controls.The 14 exons of the LBR gene were subjected to PCR amplification and Sanger sequencing.Suspected mutations were verified in other family members and 100 healthy controls.Polyphen-2 and SIFT software were used to predict the effect of the mutation,and Swiss-model software was used to simulate the protein structure.Results Three patients were found to carry a c.893G>A mutation in exon 8 of the LBR gene,which resulted in substitution of the 298th amino acid residue glycine by glutamic acid(p.Gly298Glu).The same mutation was not found in healthy family members and 100 healthy controls.The mutation was predicted to be damaging.Bioinformatic simulation showed the mutation has altered the 3D structure of the LBR protein.Conclusion The c.893G>A(p.Gly298Glu)mutation in the LBR gene probably underlies the PHA in this pedigree and has enriched the spectrum of LBR gene mutations.

关 键 词：Pelger-Huёt异常 LBR基因 外显子 基因突变 

分 类 号：R73[医药卫生—肿瘤]