Identification of a novel variant (c.1-111A>G) located in GATA-1 motif of RHCE proximal promoter in two Chinese patients with the rare D-- phenotype.

IF 2.5 3区 医学 Q2 HEMATOLOGY
Transfusion Pub Date : 2025-03-23 DOI:10.1111/trf.18223
Ran Zhang, Jizhi Wen, Changjiu Tang, Shuangshuang Jia, Qi Chen, Yanli Ji
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引用次数: 0

Abstract

Background: D-- is a rare phenotype lacking the expression of the C, c, E, and e antigens and several high-frequency antigens on the red cells. Anti-Rh17 (Hr0) could be developed in individuals with the D-- phenotype to cause hemolytic transfusion reactions (HTR) and hemolytic disease of the fetus and newborn (HDFN). Nuleotide(s) change of the RHCE gene and RHCE-D-CE hybrid alleles are the common molecular basis of the D-- phenotype.

Study design and methods: One D-- Chinese patient detected in routine RhD and RhCE serologic testing and another D-- Chinese patient identified with anti-Rh17 were recruited. Further RHD, RHCE, and RHAG whole gene sequences were analyzed using the PacBio sequencing. A dual-luciferase reporter assay was performed to verify the effect of the variant identified in the promoter of the RHCE gene on the transcriptional activity of the reporter gene in vitro.

Results: A homozygous RHCE*Ce(1-111G)/Ce(1-111G) genotype and a heterozygous RHCE*CeN.08/Ce(1-111G) genotype carried one novel variant (c.1-111A>G) located in the GATA-1 motif of the RHCE proximal promoter was identified in two D-- patients, respectively. In the reporter assay, the luciferase transcriptional activity of the mutant RHCE promoter [c.1-111G] construct reduced from ~1.0 to 0.28 relative luciferase activity normalized to RHCE wild-type, with a ~72% reduction rate.

Conclusion: The novel variant of the GATA-1 motif of the RHCE proximal promoter was identified to diminish the binding of the GATA-1 transcription factor and markedly down-regulate the transcription activity of the RHCE gene to abolish the expression of RhCE antigens, causing the rare D-- phenotype.

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来源期刊
Transfusion
Transfusion 医学-血液学
CiteScore
4.70
自引率
20.70%
发文量
426
审稿时长
1 months
期刊介绍: TRANSFUSION is the foremost publication in the world for new information regarding transfusion medicine. Written by and for members of AABB and other health-care workers, TRANSFUSION reports on the latest technical advances, discusses opposing viewpoints regarding controversial issues, and presents key conference proceedings. In addition to blood banking and transfusion medicine topics, TRANSFUSION presents submissions concerning patient blood management, tissue transplantation and hematopoietic, cellular, and gene therapies.
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