Rhnull blood group caused by novel base deletion and comprehensive pedigree analysis

IF 4.8 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-02-06 DOI:10.1016/j.intimp.2024.113993

Zhu Xiaoli , Qi Xi , Gao Hongjun , Zhu Ziqing , Sha Yuxuan , Qin Yi , Li Anming , Zhu Jianfeng , Sha Yayun , Han Junling , Gao Lingbao

{"title":"Rhnull blood group caused by novel base deletion and comprehensive pedigree analysis","authors":"Zhu Xiaoli , Qi Xi , Gao Hongjun , Zhu Ziqing , Sha Yuxuan , Qin Yi , Li Anming , Zhu Jianfeng , Sha Yayun , Han Junling , Gao Lingbao","doi":"10.1016/j.intimp.2024.113993","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>The objective of this study was to rigorously investigate and elucidate the genetic mechanisms underlying the formation of the RH<sub>null</sub> blood group in a specific case and to systematically analyse the RH blood group genes among the family members of the proband.</div></div><div><h3>Methods</h3><div>Serological methods were used to determine the RH blood group phenotype of the proband. To elucidate the underlying genetic mechanism responsible for the RH<sub>null</sub> phenotype, a comprehensive approach was undertaken, including RHCE genotyping, sequencing of RHD and RHCE genes, and exon sequencing of RHAG. For a comparative analysis, the same methodologies were applied to two family members of the proband.</div></div><div><h3>Results</h3><div>The genotype of the proband was determined as <em>CcDEe</em>. Subsequent RHAG exon sequencing analysis revealed a homozygous frameshift mutation in exon 5. Specifically, a nucleotide deletion at position c.732 in RHAG resulted in an amino acid substitution from phenylalanine to serine, followed by a frameshift and premature termination at codon 245 (p.Phe245Serfs*16). This mutation was confirmed as a novel genetic variant in the NCBI database.</div><div>Furthermore, serological findings, genotyping results, and RHAG exon sequencing data obtained from the proband’s sister were identical to those of the proband. In contrast, the proband’s son exhibited a serological phenotype of CCDee with a corresponding genotyping result for <em>CCDee.</em> RHAG exon sequencing of the son revealed a heterozygous frameshift mutation, which was consistent with the findings observed in the proband.</div></div><div><h3>Conclusion</h3><div>A novel mutation, specifically c.732delC, was identified in RHAG. The RH<sub>null</sub> phenotype observed in this subject was attributed to a homozygous frameshift mutation in this gene. This mutation results in a truncated and nonfunctional RHAG protein, which subsequently disrupts the expression of other RH antigens on the cell membrane. Therefore, the serological phenotype associated with this genetic anomaly was classified as RH<sub>null</sub>.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 113993"},"PeriodicalIF":4.8000,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1567576924025153","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

The objective of this study was to rigorously investigate and elucidate the genetic mechanisms underlying the formation of the RH_null blood group in a specific case and to systematically analyse the RH blood group genes among the family members of the proband.

Methods

Serological methods were used to determine the RH blood group phenotype of the proband. To elucidate the underlying genetic mechanism responsible for the RH_null phenotype, a comprehensive approach was undertaken, including RHCE genotyping, sequencing of RHD and RHCE genes, and exon sequencing of RHAG. For a comparative analysis, the same methodologies were applied to two family members of the proband.

Results

The genotype of the proband was determined as CcDEe. Subsequent RHAG exon sequencing analysis revealed a homozygous frameshift mutation in exon 5. Specifically, a nucleotide deletion at position c.732 in RHAG resulted in an amino acid substitution from phenylalanine to serine, followed by a frameshift and premature termination at codon 245 (p.Phe245Serfs*16). This mutation was confirmed as a novel genetic variant in the NCBI database.

Furthermore, serological findings, genotyping results, and RHAG exon sequencing data obtained from the proband’s sister were identical to those of the proband. In contrast, the proband’s son exhibited a serological phenotype of CCDee with a corresponding genotyping result for CCDee. RHAG exon sequencing of the son revealed a heterozygous frameshift mutation, which was consistent with the findings observed in the proband.

Conclusion

A novel mutation, specifically c.732delC, was identified in RHAG. The RH_null phenotype observed in this subject was attributed to a homozygous frameshift mutation in this gene. This mutation results in a truncated and nonfunctional RHAG protein, which subsequently disrupts the expression of other RH antigens on the cell membrane. Therefore, the serological phenotype associated with this genetic anomaly was classified as RH_null.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

新型碱基缺失致Rhnull血型及综合家系分析。

目的：本研究的目的是严格调查和阐明在特定情况下RH血型形成的遗传机制，并系统地分析先证家庭成员中的RH血型基因。方法：采用血清学方法测定先证者RH血型表型。为了阐明RHnull表型的潜在遗传机制，研究人员采用了一种综合的方法，包括RHCE基因分型、RHD和RHCE基因测序以及RHAG的外显子测序。为了进行比较分析，将相同的方法应用于先证者的两个家庭成员。结果：先证者基因型确定为CcDEe。随后的RHAG外显子测序分析显示外显子5有纯合移码突变。具体来说，在RHAG中c.732位的核苷酸缺失导致苯丙氨酸的氨基酸替换为丝氨酸，随后在密码子245处发生移码和过早终止（p.Phe245Serfs*16）。该突变在NCBI数据库中被确认为一种新的遗传变异。此外，从先证者的姐妹获得的血清学结果、基因分型结果和RHAG外显子测序数据与先证者相同。相比之下，先证者的儿子表现出CCDee的血清学表型和相应的CCDee基因分型结果。儿子的RHAG外显子测序显示一个杂合移码突变，这与先证者观察到的结果一致。结论：在RHAG中发现了一种新的突变，特别是c.732delC。在这个对象中观察到的RHnull表型归因于该基因的纯合移码突变。这种突变导致截断和无功能的RHAG蛋白，随后破坏细胞膜上其他RH抗原的表达。因此，与该遗传异常相关的血清学表型被归类为RHnull。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.