apparently RHD*01 with unexpected serology
(ISBT table: not listed)
This entry is partly characterized.
apparently standard RHD with unexpected serology,
Molecular data
Nucleotides:
Amino acids:
Hybrid allele encompassing at least one RHCE exon:
NA
Comments on the molecular basis:
- 10 exons sequenced
- no alterations at all in exon 1–10 including adjacent intronic sequences of the RHD locus
- exons 1 to 10 wild type
- "complete RHD-specific nucleotides without polymorphisms were present"
- "normal RHD in the sequence of the 10 exons and at least 10 nucleotides of the intron sequences flanking the exons"
- sequencing of all 10 exons and adjacent intron sequences
- no mutations in RHD exons, intron boundaries and promoter region
- one sample had RHAG c.808G>A, one sample had no mutations neither in RHD nor in RHAG
- no mutations in all 10 RHD exons, 20 intronic nucleotides flanking each exon, 5' and 3' untranslated regions of RHD, and the "putative cis-regulatory region of RHD"
- For 3 samples with D negative phenotype and 5 with weak D phenotype, no polymorphisms were found in the promoter region, exon and adjacent flanking regions
- Sequence of the 10 RHD exons and the promoter region
- no RHD variant was detected, but hematopoietic chimerism was responsible for an aberrant RHD copy number
- QMPSF and sequencing of RHD exons; introns were not sequenced
- QMPSF and sequencing of the 10 RHD exons
- "No mutations in coding exons, exon–intron boundaries and promoter region"
- Inno-Train genotyping kit
- 10 exons of RHD were sequenced, 2 samples heterozygous with RHef00122
- 10 exons of RHD and RHAG were sequenced
- chimera
Extracellular position of one or more amino acid substitutions:
Splicing:
Unconventional prediction methods:
Phenotype
Main D phenotype: unexpected D negative of weak D phenotype in the absence of molecular variants (last update: Jan. 8, 2021)Reports by D phenotype
- Undetailed ambiguous D phenotype
- Figure 7
- Mixed field reaction
- Discrepant D phenotype (negative or positive depending on anti-D reagents and techniques)
- Figure 7
- Mixed field reaction
- Weak D phenotype
- Figure 7
- Mixed field reaction
- DEL
- Figure 7
- Mixed field reaction
- D negative
- Figure 7
- Mixed field reaction
Other RH phenotypes: RH:
Serology with monoclonal anti-D
Antigen Density (Ag/RBC)
- 35 Ag/RBC, 1 sample
- 6437 Ag/RBC, 1 R1r sample with low antigen density, 2 monoclonal anti-D
- 7715 Ag/RBC, 1 R1r sample with low antigen density, 2 monoclonal anti-D
- 7913 Ag/RBC, 1 R1r sample with low antigen density, 2 monoclonal anti-D
- 13617 Ag/RBC, 1 R2r sample with low antigen density, 2 monoclonal anti-D
- 13879 Ag/RBC, 1 R2r sample with low antigen density, 2 monoclonal anti-D
- 13973 Ag/RBC, 1 R2r sample with low antigen density, 2 monoclonal anti-D
- 10578 Ag/RBC, 1 R0r sample with low antigen density, 2 monoclonal anti-D
- 10766 Ag/RBC, 1 R0r sample with low antigen density, 2 monoclonal anti-D
- 11421 Ag/RBC, 1 R0r sample with low antigen density, 2 monoclonal anti-D
- 11473 Ag/RBC, 1 R0r sample with low antigen density, 2 monoclonal anti-D
- Ag/RBC, 9 CDe/cDe, 9 CDe/CDe and 11 cDe/Cde samples; Ag density estimated from a measure with a single monoclonal IgG anti-D, compared to a RH:1,2,3,4,5 control sample with an antigen density assumed to be about 27.500 Ag/RBC
More phenotype data
Rhesus Similarity Index
Haplotype
Main CcEe phenotype association: Ce, but not a systematic association (last update: Jan. 6, 2021)ce | Ce | cE | CE | |
---|---|---|---|---|
ce | 5 | 30 | 4 | 0 |
Ce | 27 | 1 | 0 | |
cE | 0 | 0 | ||
CE | 0 |
Reports by CcEe phenotype
- with Ccee 9 samples
- with ce 1 sample (1 sample heterozygous with RHef00447)
- with CcEe 1 sample (heterozygous with RHef00122)
- with Ce 2 samples (2 samples, haplotype given, not patient phenotype)
- with ccEe 1 sample (heterozygous with RHef00119)
1 sample
2 samples (1 sample heterozygous with RHef00777)
6 samples
5 samples
3 samples
4 samples
4 samples
1 sample (1 sample, haplotype given, not patient phenotype)
5 samples
4 samples
15 samples
3 samples
Reports by allele association
Alloimmunization
Antibodies in carriers
Antibody specificity: D (RH1)
Summary: not relevant (last update: Jan. 6, 2021)Detailed information
-
Fichou Y et al. Transfusion (2018)
- Ab specificity: D (RH1)
- Number (auto- or allo-): 1
- Number listed as allo-:
- Number listed as auto-:
- Number of carriers of the allele assessed:
- DAT: negative
- Autologuous control: negative
- Elution: ND
- Autoadsorption: ND
- Titer: 4
- Was anti-LW excluded?: ND
- Other antibodies detected: non
- Cross matches (with Ab and RBCs from different partial types): ND
- Transfusion history: transfused with D+ RBC units 4 or 5 years before Ab screening test
- Pregnancy history:
- Anti-D Ig history: ND, probably none
- Context: postnatal patient
- Hemolytic consequences: no HDN; baby's DAT was negative
- Comment:
Antibodies in D negative recipients
Alloimmunization in recipients: yes, see detailed reports and phenotype data
Reports
Summary: frequent descriptions, described in all populations (last update: June 12, 2020)Detailed reports
- 1/8442 (1 of the 5 donors who were really weakly D positive) 8442 donors with D negative phenotype, screened for presence of the RHD gene in two surveys; 754 donors were C and/or E positive, the rest were ccee phenotype; 5 donors were revealed to be weakly D positive in the German population (Baden-Wurttemberg)
- 0/738 samples with D negative, but C and/or E positive phenotype, screened for RHD specific sequences (in the 5'UTR region, exon 3 and exon 10) in the Austrian population, Tyrol
- 0/104 samples with D negative, but C and/or E positive phenotype, screened for RHD specific sequences (in the 5'UTR region, exon 3 and exon 10) in the Swiss population, Bern and the canton of Bern
- 8/400 samples with D negative, but C and/or E positive phenotype, screened for RHD specific sequences (in the 5'UTR region, exon 3 and exon 10) in the German (states of Lower Saxony, Saxony- Anhalt, Thuringia, Oldenburg, and Bremen) population
- 0/71 samples with D negative, but C and/or E positive phenotype, screened for RHD specific sequences (in the 5'UTR region, exon 3 and exon 10) in the Russian (Kirov Oblast) population
- 1/333 samples with D negative, but C and/or E positive phenotype, screened for RHD specific sequences (in the 5'UTR region, exon 3 and exon 10) in the Slovenian population
- 0/54 samples with D negative, but C and/or E positive phenotype, screened for RHD specific sequences (in the 5'UTR region, exon 3 and exon 10) in the German (city of Braunschweig and eastern parts of Lower Saxony) population
- 1/55 (newborn with a strong positive DAT due to maternal anti-D that interferred with serology) 55 discrepant or weak D phenotypes among 33864 multiethnic patients (of African, Asian, Indoasian and European extraction) in the Canadian (Toronto) population
- 2/32 weak D phenotype or discordant between tube and IAT whithin a population of 305572 Chinese Han and minority donors Chinese Han
- 28/191 (16 donors and 12 patients) among 191 samples with weak D expression or unclear D phenotype within 44,743 donors and 8,604 patients tested in the Austrian population, Upper Austria
- 1/1113 pregnant D negative women tested for fetal non invasive genotyping, RHD exons 5 and 7 in the German population
- 1/96 among almost 3 million blood donations, 621685 had D negative phenotype; 46133 donors were first time donors with D negative phenotype and, when tested, 96 had RHD intron 4 in the German population
- 5/25 donors with "weak D or questionnable D status" explored by NGS to compare with Sanger sequencing in the Austrian population, Upper Austria
- 1/239 (heterozygous with RHef00447) among 2007 unrelated donors, 239 phenotyped as D negative were tested for RHD Intron 4 and Exon 10 in the Brazilian population, mainly racially mixed non-white skin color individuals, Sao Paulo
- 2/16 among 2007 unrelated donors, 16 with weak D phenotype in the Brazilian population (Sao Paulo, mainly racially mixed non-white skin color individuals)
- 65/748 among 748 individuals with D anomaly (weak or discrepant D phenotype or anti-D in individuals with D positive phenotype), 459 had D variants "that could be named weak D" (including alleles RHef00313, RHef00317 and RHef00318, as well as RHef00197 and RHef00283), 138 had partial D, 65 had no variant, 86 were not persued further (two variant alleles or incomplete or pending analysis) in the French population
- 1/520 among 520 donors with D negative phenotype, C and/or E positive in the Brazilian population, Sao Paulo
- 2/2027 2027 donors with D negative phenotype, C and/or E positive, screened for RHD exons 4, 5 and 10 and for DEL phenotype in the Australian population
- 9/58 within a donor population of 38836, 4272 initially typed D negative and 58 of these were found to be weak D with different reagents Albanian
- 3/37782 270 women with variant alleles among 37782 women with D negative phenotype, tested by quantitative fetal RHD genotyping designed to detect RHD exons 5 and 7 in the Dutch population
- 37/223 (including 1 heterozygous with RHef00183) donors with D negative phenotype initially, found to have D antigen expression (67 of the 223 samples of the cohort) or samples referred with discrepant or weak D typing, or discrepancies with previous typings, or anti-D in D positive individuals (156 of the 223 samples of the cohort) in the Indian population
- 2/26 (1 had RHAG c.808G>A, the other had normal RHAG) 26 samples with weak D phenotype, analyzed by NGS Caucasian, in the UK population, Bristol
- 3/23 (2 heterozygous, one with RHD-CE(7)-D the other with RHD(V270A)) donors with weak D phenotype (among 4458 random donors, 4028 types D positive including 19 weak D phenotype, 420 typed D negative including 4 showed to be weak D by further serological testing; in total 23 donors had weak D phenotype) in the Maroccan population
- 11/61 donors with weak D phenotype Serbia
- 5/231 231 donors with weak D phenotype in the Argentinean population, Northwestern Argentina
- 3/526 among donors with D negative phenotype, C and/or E positive, tested for presence of the RHD gene in the Argentinean population (Northwestern Argentina)
- 29/273 donors with weak D phenotype in the Brazilian population
- 23/129 (12 hemizygous, 8 homozygous, 3 heterozygous with RHef00122) donors with weak D phenotype Thai
- 1/18537 18537 donors with D negative phenotype, were tested for the presence of RHD DNA sequences, 154 samples were positive for one or several RHD exons in the Swiss population
- 2/163 selected variants included for the development of a genotyping assay mainly in the Dutch population (samples may have been included in other studies)
- 36/430 among samples with ambigous D phenotype in the French population (Table S1)
-
3/26243 donors with D negative phenotype in three studies with different inclusion criteria in the Swiss population, Zurich and Bern
(study may overlap with
24679597 ) -
1/25370 donors with D negative phenotype, screened for RHD exons 3 or 7, plus 5 and 10 in the Swiss population
(study may overlap with
24656493 ) - 1/16,253 (heterozygous with RHef00315) samples of pregnant women with D negative of weak D (2+ or less), screened for fetal RHD in the Finnish population
- 4/6523 D negative donors underwent molecular screening for RHD exons 7 and 10 (RHD sequences were detected in 23/6523) in the Croatian population
Allele or phenotype frequency
- 1/1807 (CI: 1/969 - 1/4399) estimated allele frequency in samples with D negative phenotype but C and/or E positive, screened for RHD specific sequences (in the 5'UTR region, exon 3 and exon 10) in the German (states of Lower Saxony, Saxony- Anhalt, Thuringia, Oldenburg, and Bremen) population
- 1/7641 (CI: 1/1436 - 1/149823) estimated allele frequency in samples with D negative phenotype but C and/or E positive, screened for RHD specific sequences (in the 5'UTR region, exon 3 and exon 10) in the Slovenian population
- allele not observed, lowest estimate: 1/5646 estimated allele frequency in samples with D negative phenotype but C and/or E positive, screened for RHD specific sequences (in the 5'UTR region, exon 3 and exon 10) in the Austrian (state of Tyrol) population
- 1/160 calculated allele frequency among donors with D negative and C and/or E positive phenotype in the Croatian population
- 1/1630 calculated allele frequency among donors with D negative phenotype in the Croatian population
Structure mapping
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References
- Wagner FF et al. RHD positive haplotypes in D negative Europeans. BMC Genet, 2001. [Citation] [RHeference]
- Denomme GA et al. Partial D, weak D types, and novel RHD alleles among 33,864 multiethnic patients: implications for anti-D alloimmunization and prevention. Transfusion, 2005. [Citation] [RHeference]
- Gassner C et al. Presence of RHD in serologically D-, C/E+ individuals: a European multicenter study. Transfusion, 2005. [Citation] [RHeference]
- Yu X et al. Outliers in RhD membrane integration are explained by variant RH haplotypes. Transfusion, 2006. [Citation] [RHeference]
- Yan L et al. Molecular basis of D variants in Chinese persons. Transfusion, 2007. [Citation] [RHeference]
- Polin H et al. Effective molecular RHD typing strategy for blood donations. Transfusion, 2007. [Citation] [RHeference]
- Müller SP et al. The determination of the fetal D status from maternal plasma for decision making on Rh prophylaxis is feasible. Transfusion, 2008. [Citation] [RHeference]
- Flegel WA et al. Six years' experience performing RHD genotyping to confirm D- red blood cell units in Germany for preventing anti-D immunizations. Transfusion, 2009. [Citation] [RHeference]
- Stabentheiner S et al. Overcoming methodical limits of standard RHD genotyping by next-generation sequencing. Vox Sang, 2011. [Citation] [RHeference]
- Cruz BR et al. RHD alleles in Brazilian blood donors with weak D or D-negative phenotypes. Transfus Med, 2012. [Citation] [RHeference]
- Brajovich ME et al. Comprehensive analysis of RHD alleles in Argentineans with variant D phenotypes. Transfusion, 2012. [Citation] [RHeference]
- Daniels G et al. Variants of RhD--current testing and clinical consequences. Br J Haematol, 2013. [Citation] [RHeference]
- Pham BN et al. Molecular analysis of patients with weak D and serologic analysis of those with anti-D (excluding type 1 and type 2). Immunohematology, 2013. [Citation] [RHeference]
- Haer-Wigman L et al. RHD and RHCE variant and zygosity genotyping via multiplex ligation-dependent probe amplification. Transfusion, 2013. [Citation] [RHeference]
- Fichou Y et al. Establishment of a medium-throughput approach for the genotyping of RHD variants and report of nine novel rare alleles. Transfusion, 2013. [Citation] [RHeference]
- Gowland P et al. Molecular RHD screening of RhD negative donors can replace standard serological testing for RhD negative donors. Transfus Apher Sci, 2014. [Citation] [RHeference]
- Xhetani M et al. Distribution of Rhesus blood group antigens and weak D alleles in the population of Albania. Blood Transfus, 2014. [Citation] [RHeference]
- Scott SA et al. The RHD(1227G>A) DEL-associated allele is the most prevalent DEL allele in Australian D- blood donors with C+ and/or E+ phenotypes. Transfusion, 2014. [Citation] [RHeference]
- Costa S et al. RHD alleles and D antigen density among serologically D- C+ Brazilian blood donors. Transfus Med, 2014. [Citation] [RHeference]
- Crottet SL et al. Implementation of a mandatory donor RHD screening in Switzerland. Transfus Apher Sci, 2014. [Citation] [RHeference]
- Ogasawara K et al. Molecular basis for D- Japanese: identification of novel DEL and D- alleles. Vox Sang, 2015. [Citation] [RHeference]
- C Henny et al. Impact of the mandatory donor RHD screening in Switzerland Vox Sanguinis, 2016. — Abstract — [RHeference]
- Stegmann TC et al. Frequency and characterization of known and novel RHD variant alleles in 37 782 Dutch D-negative pregnant women. Br J Haematol, 2016. [Citation] [RHeference]
- McGowan EC et al. Diverse and novel RHD variants in Australian blood donors with a weak D phenotype: implication for transfusion management. Vox Sang, 2017. [Citation] [RHeference]
- Fichou Y et al. Molecular basis of weak D expression in the Indian population and report of a novel, predominant variant RHD allele. Transfusion, 2018. [Citation] [RHeference]
- Tounsi WA et al. Complete RHD next-generation sequencing: establishment of reference RHD alleles. Blood Adv, 2018. [Citation] [RHeference]
- El Housse H et al. Comprehensive phenotypic and molecular investigation of RhD and RhCE variants in Moroccan blood donors. Blood Transfus, 2019. [Citation] [RHeference]
- Trucco Boggione C et al. Characterization of RHD locus polymorphism in D negative and D variant donors from Northwestern Argentina. Transfusion, 2019. [Citation] [RHeference]
- Arnoni CP et al. Correlation among automated scores of agglutination, antigen density by flow cytometry and genetics of D variants. Transfus Apher Sci, 2019. [Citation] [RHeference]
- Guzijan G et al. Implementation of Molecular RHD Typing at Two Blood Transfusion Institutes from Southeastern Europe. Transfus Med Hemother, 2019. [Citation] [RHeference]
- Thongbut J et al. Comprehensive Molecular Analysis of Serologically D-Negative and Weak/Partial D Phenotype in Thai Blood Donors. Transfus Med Hemother, 2020. [Citation] [RHeference]
- Tammi SM et al. Next-generation sequencing of 35 RHD variants in 16 253 serologically D- pregnant women in the Finnish population. Blood Adv, 2020. [Citation] [RHeference]
- Safic Stanic H et al. D variants in the population of D-negative blood donors in the north-eastern region of Croatia. Transfus Med, 2021. [Citation] [RHeference]
Last update: Jan. 7, 2021