由RHAG基因p.R191G变异导致血清学弱D表型的遗传学分析  

Genetic analysis of a serologically weak D phenotype caused by the p.R191G variant of the RHAG gene

作　　者：章旭 李晓丰[1] 李剑平[1] ZHANG Xu;LI Xiaofeng;LI Jianping(Institute of Transfusion Medicine,Shenyang Central Blood Station(Liaoning Blood Center),Shenyang 110044,China)

机构地区：[1]沈阳中心血站/辽宁省血液中心输血医学研究所,辽宁沈阳110044

出　　处：《中国输血杂志》2024年第12期1422-1426,共5页Chinese Journal of Blood Transfusion

基　　金：沈阳市血液安全研究重点实验室,沈阳市科技创新平台建设计划项目(21-104-0-15);沈阳市公共卫生研发科技专项(24-214-3-118)。

摘　　要：目的分析1例RHAG基因变异导致血清学弱D表型的分子机制。方法对1例血清学弱D表型标本进行RHD、RHCE和RHAG基因的全编码区直接测序,并对变异位点采用生物信息学软件进行预测分析。结果该标本血清学检测结果为弱D和正常Rh Ccee表型。直接测序结果显示RHD和RHCE基因序列正常,RHAG基因检测到1个纯合子变异c.572G>A(p.R191Q)。PolyPhen2、PROVEAN和Mutation Taster算法分别预测c.572G>A变异对蛋白结构“可能有害”、“有害”和“有影响”。突变后的蛋白质稳定性自由能变化(△△G)值预测其可能影响蛋白的稳定性。三维蛋白模拟模型提示p.R191Q可造成RhAG蛋白空间结构的改变。结论由RHAG基因p.R191Q纯合子变异导致血清学弱D表达,但不影响RhCE抗原的表达。Objective To analyze the molecular mechanism of a serologically weak D phenotype caused by RHAG gene variation.Methods The full coding and flanking regions of RHD,RHCE and RHAG genes of the serologically weak D phe-notype sample were identified through direct sequencing.Bioinformatics software was used to analyze the structure of the va-riant protein.Results The serological test results were weak D and normal Rh Ccee phenotypes.Normal sequence of RHD and RHCE genes,and a homozygous variation c.572G>A(p.R191Q)of the RHAG gene were revealed by direct sequen-cing.The c.572G>A(p.R191Q)mutation was predicted to be“probably damaging”,“deleterious”and“affected”by PolyPhen2,PROVEAN and Mutation Taster algorithms,respectively.The free energy change(△△G)value predicted it to have a destabilizing effect on the RhAG protein.Meanwhile,modeling of the 3D structure predicted that the p.R191Q a-mino acid substitution may alter the space conformation of the RhAG protein.Conclusion A homozygous variation of RHAG gene p.R191Q leads to serologically weak D expression,but does not affect RhCE antigen expression.

关 键 词：血清学弱D表型 RHD基因 RHAG基因 生物信息学分析 

分 类 号：R457.11[医药卫生—治疗学]