New silent and <i>weak D</i> alleles: molecular characterization and associated antigen density

Filosa, Lugdivine; Beley, Sophie; Chiaroni, Jacques; Bailly, Pascal; Silvy, Monique

doi:10.1111/trf.13655

Cited by 3 publications

(4 citation statements)

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“…The amino acid substitutions in the overall structure of RhD protein are displayed in Figure 2A . A known mutation c.143A>G resulted in the substitution of p.Y48C ( 26 ), and two novel missense mutations led to p.G180R, and p.P261L substitutions were selected for 3D structure analysis. These three amino acid substitutions were located in α2 helix, α6 helix, and loop ICL3.…”

Section: Resultsmentioning

confidence: 99%

“…Notably, distinct phenotypes and genotypes of RhD variants have specific clinical significance and require blood transfusion strategies ( 28 , 29 ). The RhD blood type mismatch between donor and recipient may cause acute severe immune response resulting in neonatal hemolytic disease, hemolytic transfusion reaction, and autoimmune hemolytic disease ( 26 , 30 ). Therefore, genotyping is required to determine the molecular characteristics of RhD variant donors or recipients, which is beneficial to disease treatment.…”

Section: Discussionmentioning

confidence: 99%

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The Significance of RHD Genotyping and Characteristic Analysis in Chinese RhD Variant Individuals

et al. 2021

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BackgroundRhD is the most important and complex blood group system because of its highly polymorphic and immunogenic nature. RhD variants can induce immune response by allogeneic transfusion, organ transplantation, and fetal immunity. The transfusion strategies are different for RhD variants formed by various alleles. Therefore, extensive investigation of the molecular mechanism underlying RhD variants is critical for preventing immune-related blood transfusion reactions and fetal immunity.MethodsRhD variants were collected from donors and patients in Zhejiang Province, China. The phenotypes were classified using the serologic method. The full coding regions of RHD gene were analyzed using the PCR-SBT method. The multiplex ligation-dependent probe amplification (MLPA) assay was used to analyze the genotype and gene copy number. SWISS-MODLE and PyMOL software were used to analyze 3D structures of RhD caused by the variant alleles. The effect of non-synonymous substitutions was predicted using Polymorphism Phenotyping algorithm (PolyPhen-2), Sorting Intolerant From Tolerant (SIFT), and Protein Variation Effect Analyzer (PROVEAN) software.ResultsIn the collected RhD variants, 28 distinct RHD variant alleles were identified, including three novel variant alleles. RH-MLPA assay is advantageous for determining the copy number of RHD gene. 3D homology modeling predicted that protein conformation was disrupted and may explain RhD epitope differential expression. A total of 14 non-synonymous mutations were determined to be detrimental to the protein structure.DiscussionWe revealed the diversity of RHD alleles present in eastern Chinese RhD variants. The bioinformatics of these variant alleles extended our knowledge of RhD variants, which was crucial for evaluating their impact to guide transfusion support and avoid immune-related blood transfusion reactions.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Significance of RHD Genotyping and Characteristic Analysis in Chinese RhD Variant Individuals

et al. 2021

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“…After control of amplification on 1.5% (wt/vol) agarose gel, PCR products were sequenced by Eurofins Genomics (Paris, France). The sequences of primer sets used for RHD exon amplification have been previously described 15,16 …”

Section: Methodsmentioning

confidence: 99%

“…The sequences of primer sets used for RHD exon amplification have been previously described. 15,16 3 | RESULTS In total, 76 samples (85%) had at least one RHCE variant allele. Fifteen individuals (17%) presented either two variant alleles.…”

Section: Exon Amplification and Sequencingmentioning

confidence: 99%

Frequency and characterization of RHD and RHCE variants in the Noir Marron population from French Guiana

et al. 2022

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Background The RH system is one of the most polymorphic blood group systems due to the proximity and opposite orientation of RHD and RHCE genes. Numerous alleles are described and can affect Rh protein expression. This complexity is especially evident in populations of African origin. We performed RHD and RHCE genotyping of the Noir Marron population in French Guiana. This population belongs to the Maroon community who are direct descendants of African slaves, who escaped from Dutch plantations, in the current day Suriname, during the 17th century. They represent an original ethnic group with highly blended culture. Methods and materials A total of 89 DNA samples were collected from four different ethnic groups of the Noir Marron population of French Guiana. RHD and RHCE genotyping was performed using DNA microarray and/or sequencing. Results and discussion Significant allelic diversity was shown, with 45% of individuals presenting an RHD gene variant (most common: RHD*DAU, RHD*DIVa, and RHD*DIIIa allele) and 9.4% with a partial D phenotype. Likewise, 85% presenting an RHCE gene variant and 9% a partial RH2 antigen. One original allele was identified in two D+ Noir Marron individuals: a hybrid RHD*DIIIa‐CE(9)‐D allele, encoding probably a partial D antigen and associated with an RHCE*ce(48C,733G,1006T) allele. The African diversity of RHD and RHCE genes is found in this population with preserved genetic but mixed cultural backgrounds. These data allow us to describe the characteristics of the RH system antigen and highlights a significant number of partial antigens with a risk of alloimmunization.

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Weak D Type 102 Found in a Family Study: The First Case in Korea

Lee

Chung

et al. 2020

KJBT

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Weak D type 102 allele (RHD*01W.102) carrying a missense variant (c.73A＞T, p.Ile25Phe) in exon 1 of the RHD has not been reported in Koreans to date. This is the first report of the weak D type 102 allele in the Korean population. The proposita, a 35-year-old woman, showed a serological weak D phenotype in routine RhD typing. Sequencing of all 10 RHD exons and zygosity testing targeting the hybrid Rhesus box revealed this proposita to harbor the weak D type 102 allele, as well as an RHD deletion (RHD*01W.102/RHD*01N.01). Family studies showed that the weak D type 102 allele was also present in her father and older brother (both assumed to be RHD*01W.102/RHD*01) but not in her mother and oldest brother (both assumed to be RHD*01/RHD*01N.01). In silico analysis of the replacement of isoleucine by phenylalanine at position 25 was done with PolyPhen-2, SIFT, and PROVEAN. While PolyPhen-2 predicted the variant as benign, SIFT and PROVEAN predicted it as damaging and deleterious, respectively, suggesting RHD c.73A>T (I25F) as the cause of serologic weak D phenotype. This patient should be treated as D-negative, when transfusion is needed.

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New silent and weak D alleles: molecular characterization and associated antigen density

Cited by 3 publications

References 5 publications

The Significance of RHD Genotyping and Characteristic Analysis in Chinese RhD Variant Individuals

The Significance of RHD Genotyping and Characteristic Analysis in Chinese RhD Variant Individuals

Frequency and characterization of RHD and RHCE variants in the Noir Marron population from French Guiana

Weak D Type 102 Found in a Family Study: The First Case in Korea

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