RHD*15 - RHD*weak partial 15
(ISBT table: RHD partial D v5.0)
This entry is an RHD allele.
RHD(G282D), RHD*845A, RHD*845A (weak partial D type 15), RHD*845G>A, partial weak D type 15, weak partial D type 15,
Molecular data
Nucleotides:
845G>A;
Amino acids: G282D;
Hybrid allele encompassing at least one RHCE exon:
no
Comments on the molecular basis:
Extracellular position of one or more amino acid substitutions:
- considered to be extracellular
- none of the mutations are predicted to affect an extracellular amino acid
- membrane localization: TM
- considered to be extracellular; Table S3
Splicing:
Unconventional prediction methods:
Phenotype
Main D phenotype: very weak (last update: Dec. 28, 2020)Reports by D phenotype
- D positive (apparently normal D or undetailed positive D)
- Undetailed ambiguous D phenotype
- Discrepant D phenotype (negative or positive depending on anti-D reagents and techniques)
- Weak D phenotype
- Very weak D phenotype
- DEL
- D negative
Other RH phenotypes: RH:-2, -3, -5,
Serology with monoclonal anti-D
- 2 anti-D non-reactive with variant, out of 22 monoclonal IgG tested; adsorption-elution was performed (Table 2)
- tested with a panel of anti-D but results not detailed
- results are not detailed per Ab or per variant
- more than 10 monoclonal IgG anti-D non-reactive with variant, out of 60 monoclonal IgG anti 22 IgM anti-D tested
- 0 monoclonal IgG anti-D non-reactive with variant, 13 anti-D tested (Data S1)
- (Table 1)
- reactions: (+) or -, with a panel of 10 monoclonal anti-D
Antigen Density (Ag/RBC)
More phenotype data
Haplotype
Main CcEe phenotype association: cE is the most frequent association, ce is less frequent (last update: Jan. 8, 2021)ce | Ce | cE | CE | |
---|---|---|---|---|
ce | 1 | 15 | 107 | 0 |
Ce | 3 | 14 | 1 | |
cE | 39 | 0 | ||
CE | 1 |
Reports by CcEe phenotype
- with Ce 3 samples (haplotype given, not complete phenotype; not all samples could be counted)
- with cE 6 samples
- with CE 1 sample (haplotype given, not complete phenotype; not all samples could be counted)
- with Ccee 2 samples
- with CcEe 7 samples
- with CCEe 1 sample
- with ce 1 sample
- with ccEe 2 samples (2 samples used as controls, may have been included in other studies) (2 samples also included in
1 sample (haplotype given, not complete complete phenotype) (haplotype given, not complete phenotype; not all samples could be counted)
2 samples (at least 2 samples; haplotype given, not complete phenotype)
10 samples (9 also included in
9 samples (9 samples also included in
11 samples (haplotype listed, not complete phenotype)
0 samples (haplotype listed, not complete phenotype; presented as a general association)
4 samples
8 samples
1 sample (considering RHCE genotyping, RHD zygosity and RHD allele, R1 was considered the most likely haplotype)
4 samples (2 heterozygous with RHef00448)
2 samples (2 homozygous samples)
1 sample (some samples probably also included in
7 samples (2 samples also included in
46 samples
13 samples
1 sample (considering RHCE genotyping, RHD zygosity and RHD allele, R2 was considered the most likely haplotype)
3 samples
12 samples
14 samples
9 samples
Reports by allele association
Alloimmunization
Antibodies in carriers
Antibody specificity: D (RH1)
Summary: probably allo-anti-D (last update: Dec. 28, 2020)Detailed information
-
Wagner FF et al. Blood (2000)
- Ab specificity: D (RH1)
- Number (auto- or allo-):
- Number listed as allo-: 1
- Number listed as auto-:
- Number of carriers of the allele assessed: 1
- DAT: ND
- Autologuous control: ND
- Elution: negative
- Autoadsorption: ND
- Titer: 1
- Was anti-LW excluded?: ND
- Other antibodies detected: none
- Cross matches (with Ab and RBCs from different partial types): ND
- Transfusion history: ND
- Pregnancy history:
- Anti-D Ig history: ND, probably none
- Context: ND
- Hemolytic consequences: ND
- Comment: "reports of the Rhesus Immunization Registery as of June 2006"
Wagner FF et al. Transfus Med Hemother (2014) (RIR n°11)
Flegel WA et al. Curr Opin Hematol (2006) (some samples overlap with other reports)
-
Pham BN et al. Immunohematology (2013)
- Ab specificity: D (RH1)
- Number (auto- or allo-):
- Number listed as allo-: 1
- Number listed as auto-:
- Number of carriers of the allele assessed: 17
- DAT: negative
- Autologuous control: negative
- Elution: negative
- Autoadsorption: not autoadsorbable
- Titer: ND
- Was anti-LW excluded?: ND
- Other antibodies detected: ND
- Cross matches (with Ab and RBCs from different partial types): ND
- Transfusion history: ND
- Pregnancy history:
- Anti-D Ig history: ND
- Context: ND
- Hemolytic consequences: ND
- Comment:
-
Takeuchi-Baba C et al. Transfusion (2019)
- Ab specificity: D (RH1)
- Number (auto- or allo-): 0
- Number listed as allo-:
- Number listed as auto-: 1
- Number of carriers of the allele assessed:
- DAT: negative (throughout the entire observation period)
- Autologuous control:
- Elution: anti-D (at 3, 6, 12, and 24 months after transfusion); "the eluates obtained from D-positive (R2R2) cells or D-negative (rr) cells sensitized by the patient’s serum reacted well with R2R2 cells (Table 2), whereas eluates from D-negative (rr) cells sensitized with alloanti-D did not agglutinate R2R2 cells"
- Autoadsorption: Anti-D was adsorbable on autologous, RHef00283, RHef00295, RHef00093, D positive and D- negative RBCs.
- Titer:
- Was anti-LW excluded?: excluded
- Other antibodies detected:
- Cross matches (with Ab and RBCs from different partial types):
- Transfusion history:
- Pregnancy history:
- Anti-D Ig history:
- Context:
- Hemolytic consequences: no signs of delayed hemolytic reaction
- Comment: auto-anti-D detected 3 months after transfusion in a Japanese individual, persisted for 24 months
-
Daniels G et al. Br J Haematol (2013)
(review; Table I)
- Ab specificity: D (RH1)
- Number (auto- or allo-):
- Number listed as allo-: no new case detailed (listed as allo-anti-D)
- Number listed as auto-: NA
- Number of carriers of the allele assessed: NA
- DAT: NA
- Autologuous control: NA
- Elution: NA
- Autoadsorption: NA
- Titer: NA
- Was anti-LW excluded?: NA
- Other antibodies detected: NA
- Cross matches (with Ab and RBCs from different partial types): NA
- Transfusion history: NA
- Pregnancy history:
- Anti-D Ig history: NA
- Context: NA
- Hemolytic consequences: NA
- Comment: list of D variants associated with alloanti-D formation
Antibodies in D negative recipients
Alloimmunization in recipients: expected to be possible, see phenotype data
Reports
Summary: common allele, mainly in individuals of Eastern Asian descent, or compatible with such descent; also detected in several European populations (individuals of Eastern Asian descent?) (last update: Dec. 28, 2020)Detailed reports
- 0/161 random donors with weak D phenotype; DVI samples were excluded by serologic testing in the German population (Southwestern Germany), White
- 1 sample in the German or Austrian population
- 1/3 samples with weak D phenotype in the Chinese population
- 1/168 among 168 samples referred for weak D phenotype and/or allo anti-D in D positive individuals, 137 were characterized in the study (70 by serology, 67 by molecular analysis, 31 could not be typed because serologic typing was inconclusive and molecular typing could not be performed) in the French population (Caucasian)
- 1/23 121022 donors tested: 201 had weak D phenotype and, among those, 23 very weak D phenotype German
- 18/56 weak D phenotype Chinese Han
- 1/45 45 samples referred for D typing discrepancies in the USA population (Table 2)
- 2/4 weak D phenotype Korean (South Korea)
- 1/126 donors with D negative phenotype Korean (South Korea)
- 11/32 weak D or discordant between tube and IAT whithin a population of 305572 Chinese Han and minority donors Chinese Han
- 17/289 289 samples with ambiguous D phenotype (333 consecutive samples with ambiguous D phenotype studied but 44 were hybrid alleles, excluded from the study) in the French (Western France) population
- 1/101 donors with weak D phenotype Danish
- 1/50 donors with D negative phenotype Han Chinese
- 1/167 discrepant D testing results (donors?) Croatian
- 2/34 DEL donors from a total of 30799 blood samples tested Chinese Anhui Han
- 5/163 selected variants included for the development of a genotyping assay mainly in the Dutch population (samples may have been included in other studies)
- 1/430 among samples with ambigous D phenotype in the French population (Table S1)
- 12/31200 consecutive donors with D negative phenotype, tested for presence of RHD intron 4, exon 7 and/or exon 10 in the Polish population
- 1/50 50 weak D phenotypes among 1113 samples, initially with D negative phenotype (25 samples were not resolved by the genotyping performed) in the Egyptian population
- 17/748 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
- 64/2493 (62 heterozygous with RHef00446, 2 heterozygous with RHef00122) donors with apparent D negative phenotype (108/2493 were in fact weak D or DEL) Han Chinese (Shanxi Province, Central China)
- 13/32 donors suspected to have weak D or partial D phenotypes sent to a reference laboratory Chinese (Zhejiang Han)
- 1/627 weak D typing (95% from patients, 5% from donors; 21,2% were identified as RHef00442 or RHef00446 by authors, "mostly (…) inconclusive serology consequent to recent transfusion") in the Belgian (Flanders) population
-
12/45 among 763408 donors, after ruling out partial D phenotypes by using 5 monoclonal anti-D, 75 were considered weak D phenotype and 45 were genotyped Japanese
(12 samples in common with
27183894 ) - 12/37782 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
-
36/226 226 donors considered weak D phenotype, after ruling out partial D phenotypes by using 5 monoclonal anti-D Japanese
(12 samples in common with
26340140 ) - 2/110 among members of the RhD-negative club Korean
- 2/100 donors with weak D phenotype Australia
- 1/200 donors with D negative phenotype, tested by MPLA Chinese, Southern Han
- 4/62 (1 heterozygous with RHef00122) D variant donors Chinese, Southern Han
- 1/662 among 662 pregnant patients with apparent D negative phenotype, enroled for fetal genotyping Australia
- 1/662 among 662 pregnant patients with apparent D negative pheotype, enroled for fetal genotyping in the Australian population
- 2/61 donors with apparent D negative phenotype, C and/or E positive Serbia
- 1/61 donors with weak D phenotype Serbia
- 1/64 among 175000 donors, 64 had weak D phenotype and underwent molecular identification in the Greek population
- 18/45 (including 1 heterozygous with RHef00122 and 1 with RHef00232) among 132479 donors screened for serologic weak D phenotype in the northeastern Chinese Liaoning Province population
- 3/129 (2 hemizygous, 1 heterozygous with RHef00122) donors with weak D phenotype Thai
- 1/121 (heterozygous with RHef00448) donors with DEL phenotype Thai
- 1/185 RH:–1,–4 or RH:–1,–5 recipients reported by a French lab
- 1/353 samples referred for discrepant or weak D typing in the USA population
- 2/16,253 samples of pregnant women with D negative of weak D (2+ or less), screened for fetal RHD in the Finnish population
- 1 hemizygote among 278 samples selected for the development of nonspecific quantitative next-generation sequencing. (non-random samples, may have been reported in other studies)
Allele or phenotype frequency
- "rare" estimated prevalence in the German population
- "about 70% weak D phenotypes were RHef00283" among 400253 random donors, 1585 had apparent D negative phenotype, but among those, 279 were DEL and 69 were "typed as weak or partial D" in the Chinese (Shanghai) population
- 1/2600 (CI: 1/1605 - 1/4506) estimated allele frequency in individuals with D negative phenotype in the Polish population
- 0.0094 allele frequency in 106 donors with weak D phenotype Brazilian (mixed origin, mainly between African and European descent)
- 0.00096 calculated allele frequency in the northeastern Chinese Liaoning Province population
- 0.012 calculated in 16,253 samples of pregnant women with D negative of weak D (2+ or less), screened for fetal RHD in the Finnish population
Structure mapping
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References
- International Society of Blood Transfusion et al. International Society of Blood Transfusion (ISBT) allele table Online ressource, 1935. — Online ressource — [RHeference]
- Wagner FF et al. Molecular basis of weak D phenotypes. Blood, 1999. [Citation] [RHeference]
- Wagner FF et al. Weak D alleles express distinct phenotypes. Blood, 2000. [Citation] [RHeference]
- Legler TJ et al. RHD sequencing: a new tool for decision making on transfusion therapy and provision of Rh prophylaxis. Transfus Med, 2001. [Citation] [RHeference]
- Shao CP et al. Molecular background of Rh D-positive, D-negative, D(el) and weak D phenotypes in Chinese. Vox Sang, 2002. [Citation] [RHeference]
- Lin IL et al. Molecular basis of weak D in Taiwanese. Ann Hematol, 2003. [Citation] [RHeference]
- Ansart-Pirenne H et al. RhD variants in Caucasians: consequences for checking clinically relevant alleles. Transfusion, 2004. [Citation] [RHeference]
- Körmöczi GF et al. Novel weak D types 31 and 32: adsorption-elution-supported D antigen analysis and comparison to prevalent weak D types. Transfusion, 2005. [Citation] [RHeference]
- Doescher A et al. Weak D type 1.1 exemplifies another complexity in weak D genotyping. Transfusion, 2005. [Citation] [RHeference]
- Sun GD et al. [Molecular background of weak D type 15 as the predominant weak D type found in Chinese population]. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2006. [Citation] [RHeference]
- Luettringhaus TA et al. An easy RHD genotyping strategy for D- East Asian persons applied to Korean blood donors. Transfusion, 2006. [Citation] [RHeference]
- Flegel WA et al. How I manage donors and patients with a weak D phenotype. Curr Opin Hematol, 2006. [Citation] [RHeference]
- Westhoff CM et al. Rh complexities: serology and DNA genotyping. Transfusion, 2007. [Citation] [RHeference]
- Le Maréchal C et al. Identification of 12 novel RHD alleles in western France by denaturing high-performance liquid chromatography analysis. Transfusion, 2007. [Citation] [RHeference]
- Yan L et al. Molecular basis of D variants in Chinese persons. Transfusion, 2007. [Citation] [RHeference]
- Li Q et al. Molecular basis of D variants between Uigur and Han blood donors in Xinjiang. Transfus Med, 2008. [Citation] [RHeference]
- Christiansen M et al. Correlation between serology and genetics of weak D types in Denmark. Transfusion, 2008. [Citation] [RHeference]
- Li Q et al. Molecular basis of the RHD gene in blood donors with DEL phenotypes in Shanghai. Vox Sang, 2009. [Citation] [RHeference]
- Dogic V et al. Distribution of weak D types in the Croatian population. Transfus Med, 2011. [Citation] [RHeference]
- Chen Q et al. Molecular basis of weak D and DEL in Han population in Anhui Province, China. Chin Med J (Engl), 2012. [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]
- Daniels G et al. Variants of RhD--current testing and clinical consequences. Br J Haematol, 2013. [Citation] [RHeference]
- Orzińska A et al. RHD variants in Polish blood donors routinely typed as D-. Transfusion, 2013. [Citation] [RHeference]
- Hussein E et al. Weak D types in the Egyptian population. Am J Clin Pathol, 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]
- Wagner FF et al. The Rhesus Site. Transfus Med Hemother, 2014. [Citation] [RHeference]
- Ye SH et al. A comprehensive investigation of RHD polymorphisms in the Chinese Han population in Xi'an. Blood Transfus, 2014. [Citation] [RHeference]
- He J et al. Molecular basis and zygosity determination of D variants including identification of four novel alleles in Chinese individuals. Transfusion, 2015. [Citation] [RHeference]
- Van Sandt VS et al. RHD variants in Flanders, Belgium. Transfusion, 2015. [Citation] [RHeference]
- Zhang X et al. [Molecular mechanism of 101A>G and 845G>A mutations of RHD gene responsible for a weak RhD]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2015. [Citation] [RHeference]
- Isa K et al. Prevalence of RHD alleles in Japanese individuals with weak D phenotype: Identification of 20 new RHD alleles. Vox Sang, 2016. [Citation] [RHeference]
- Ogasawara K et al. Weak D alleles in Japanese: a c.960G>A silent mutation in exon 7 of the RHD gene that affects D expression. Vox Sang, 2016. [Citation] [RHeference]
- Seo MH et al. An effective diagnostic strategy for accurate detection of RhD variants including Asian DEL type in apparently RhD-negative blood donors in Korea. Vox Sang, 2016. [Citation] [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]
- Ji YL et al. RHD genotype and zygosity analysis in the Chinese Southern Han D+, D- and D variant donors using the multiplex ligation-dependent probe amplification assay. Vox Sang, 2017. [Citation] [RHeference]
- S Vege et al. RHD Genotyping of Discrepant or Weak D Samples: Over a Year’s Experience. Transfusion, 2017. — Abstract — [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]
- Hyland CA et al. Non-invasive fetal RHD genotyping for RhD negative women stratified into RHD gene deletion or variant groups: comparative accuracy using two blood collection tube types. Pathology, 2017. [Citation] [RHeference]
- Dezan MR et al. High frequency of variant RHD genotypes among donors and patients of mixed origin with serologic weak-D phenotype. J Clin Lab Anal, 2018. [Citation] [RHeference]
- Jérôme Babinet et al. Erratum à l’article : « Résumés des Posters » [Transfus. Clin. Biol. 24 (2017) 3S] Transfusion Clinique et Biologique, 2018. — Abstract — [RHeference]
- Guzijan G et al. Implementation of Molecular RHD Typing at Two Blood Transfusion Institutes from Southeastern Europe. Transfus Med Hemother, 2019. [Citation] [RHeference]
- Takeuchi-Baba C et al. Production of RBC autoantibody mimicking anti-D specificity following transfusion in a patient with weak D Type 15. Transfusion, 2019. [Citation] [RHeference]
- Koutsouri T et al. Frequency distribution of RHD alleles among Greek donors with weak D phenotypes demonstrates a distinct pattern in central European countries. Transfus Med, 2019. [Citation] [RHeference]
- Zhang X et al. Molecular and computational analysis of 45 samples with a serologic weak D phenotype detected among 132,479 blood donors in northeast China. J Transl Med, 2019. [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]
- Floch A et al. Comment from Rheference Online ressource, 2020. — Online ressource — [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]
- Stef M et al. RH genotyping by nonspecific quantitative next-generation sequencing. Transfusion, 2020. [Citation] [RHeference]
- Vege S et al. Impact of RHD genotyping on transfusion practice in Denmark and the United States and identification of novel RHD alleles. Transfusion, 2021. [Citation] [RHeference]
Last update: Jan. 8, 2021