Identification of a novel frequent RHCEce308T variant allele in Chinese D- individuals, resulting in a C plus c- phenotype
Identification of a novel frequent RHCEce308T variant allele in Chinese D- individuals, resulting in a C plus c- phenotype
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在中国 D- 个体中鉴定出一种新的常见 RHCEce308T 变异等位基因，导致 C + c- 表型
DOI：
10.1111/trf.13709
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发表时间：
2016
期刊：
影响因子：
2.9
通讯作者：
van der Schoot C. Ellen
中科院分区：
文献类型：
--
作者：
Stegmann Tamara C.;Ji Yanli;Bijman Renate;Wang Zhen;Wen Jizhi;Wei Ling;Veldhuisen Barbera;Haer-Wigman Lonneke;Lighthart Peter;Loden-van Straaten Martin;Luo Guangping;van der Schoot C. Ellen
背景RHCE等位基因是高度多态性的，已经描述了60多种导致C、c、E和e抗原表达减少的变体。关于RHCE变异体在中国人群中的流行情况还知之甚少。携带变异体的个体在不匹配的妊娠或输血时有产生同种抗体的风险。在这项研究中，表型和基因分型的theRHCE等位基因在中国捐助者揭示了一个新的临床相关mutation.Study设计和METHODS血液样本从200 D-和200 D+中国捐助者进行了分析theRH多重连接依赖性探针扩增（MLPA）测定和比较血清分型RhCE表型，当可用。在基因分型结果异常的标本中，对RHCE基因的所有外显子进行测序。用MLPA法检测了6例D-型供者（6/200）的RHCE基因第2外显子的突变拷贝数，而D+型供者（0/200）的RHCE基因第2外显子的突变拷贝数均为阴性。在本研究中，对这6名供体的RHCE基因进行测序，发现了一个新的变异体RHCE * ce 308 C>T（p.103Pro>Leu）等位基因，其等位基因频率为0.015。在D+个体中未检测到这种变异，显示与D-单倍型的连锁。在供体红细胞上证明了血清学上弱的C表达和C表达的丧失。在cDe/ce和CDe/CDe成红细胞中RHCE * ce 308 T变异体的体外转染研究证实，该变异体与抗C反应性相关，同时消除c expression. CONCLUSION通过标准RHCE基因分型携带该变异体的个体的基因分型可能错误地预测C-表型或c+表型。在为中国人群设计的RHCE基因分型检测中应考虑到这种新的变异。
BACKGROUNDTheRHCEallele is highly polymorphic; more than 60 variants have been described leading to diminished expression of C, c, E, and e antigens. Not much is known about the prevalence ofRHCEvariants in the Chinese population. Individuals carrying a variant are at risk to develop alloantibodies in response to mismatched pregnancy or transfusion. In this study, phenotyping and genotyping of theRHCEallele in Chinese donors revealed a new clinically relevant mutation.STUDY DESIGN AND METHODSBlood samples from 200 D– and 200 D+ Chinese donors were analyzed by theRHmultiplex ligation–dependent probe amplification (MLPA) assay and compared to serologically typed RhCE phenotypes, when available. All exons of theRHCEgene were sequenced in samples with aberrant genotyping results. The phenotype of the new variantRHCEallele was tested by transducing cultured human erythroblasts.RESULTSAberrant copy numbers for Exon 2 of theRHCEgene were discovered by MLPA in six D– donors (6/200), but not in D+ donors (0/200). Sequencing of theRHCEgene in these six donors identified a new variantRHCE*ce308C>T(p.103Pro>Leu) allele with an allele frequency of 0.015 within the D– individuals in this study. This variant was not detected in D+ individuals showing linkage with the D– haplotype. Serologically weak C expression and loss of c expression was demonstrated on donor red blood cells. In vitro transfection studies of theRHCE*ce308Tvariant in cDe/ce and CDe/CDe erythroblasts confirmed that the variant is associated with anti‐C reactivity while abolishing c expression.CONCLUSIONGenotyping of individuals carrying this variant by standardRHCEgenotyping might falsely predict a C– phenotype or a c+ phenotype. This new variant should be taken into account inRHCEgenotyping assays designed for the Chinese population.