RHD*03.01 - RHD*DIIIa
(ISBT table: RHD partial D v5.0)
This entry is an RHD allele.
DIII type 5, DIIIa, DIIIa(BP.) (obsolete), DIIIa(DJ.) (obsolete), RHD(L62F,A137V,N152T,T201R,F223V), RHD(L62F,A137V,N152T,T201R,F223V,A273A), RHD*186T,410T,455C,602G,667G,819A, RHD*186T,410T,455C,602G,667G,819A (DIIIa),
Molecular data
Nucleotides:
186G>T; 410C>T; 455A>C; 602C>G; 667T>G; 819G>A;
Amino acids: L62F; A137V; N152T; T201R; F223V; A273A;
Hybrid allele encompassing at least one RHCE exon:
no
Comments on the molecular basis:
- initially reported as Exon 3, 455A>C; Exon 4, 602C>G; and Exon 5, 667 T>G
- reanalyzed samples from
9256293 and detected additional Exon 2, 186G>T (L62F), Exon 3, 410C>T (A137V), and a 819G>A change in Exon 6; in trans, sample BP had RHef00452 and sample DJ had RHef00442 - see also "Additional comments" section on the RhesusBase http://www.rhesusbase.info/RHDDIIItype5.htm
- "Original DIIIa report missed 186G>T, 410C>T, and 819G>A"
- reanalyzed samples from
9256293 and detected additonal Exon 2, 186G>T (L62F), Exon 3, 410C>T (A137V), and a 819G>A change in Exon 6; in trans, sample BP had RHef00452 and sample DJ had RHef00442
Extracellular position of one or more amino acid substitutions:
Splicing:
Unconventional prediction methods:
Phenotype
Main D phenotype: D positive (last update: May 16, 2020)Reports by D phenotype
Other RH phenotypes: RH:-2, -3, -10, 12, -20, -23, -30, -31, -32, -34, -42, 54, -56, 20,
Serology with monoclonal anti-D
Antigen Density (Ag/RBC)
More phenotype data
Rhesus Similarity Index
Haplotype
Main CcEe phenotype association: ce (last update: May 4, 2020)ce | Ce | cE | CE | |
---|---|---|---|---|
ce | 25 | 7 | 3 | 0 |
Ce | 0 | 0 | 0 | |
cE | 0 | 0 | ||
CE | 0 |
Reports by CcEe phenotype
- with ccEe 2 samples (2 samples could be RHef00442 associated with RHef00058 or, less likely, RHef00313 associated with RHef00056)
- with Ccee 6 samples (3 samples heterozygous with RHef00452; 3 could be RHef00442 associated with RHef00058 or, less likely, RHef00313 associated with RHef00056)
- with ce 25 samples (16 could be RHef00442 associated with RHef00058 or, less likely, RHef00313 associated with RHef00056)
- with Ce 0 samples (Table 2; no sample count, listed as general association)
1 sample
1 sample
0 samples (Figure 2; presented as a general association, no sample count) (Figure 2; presented as a general association, no sample count)
Reports by allele association
- RHCE*ce(48C,733G,1006T) (RHCE*ce.20.03)
- RHCE*48C,733G,1025T (RHCE*01.20.04.01)
- RHCE*01.20.02 (RHCE*48C,733G)
- wild type for position RHCE c.1025
- RHCE*01.20.01 (RHCE*733G)
- RHCE*01.03 (RHCE*1025T)
- RHCE*ce(48C)-D(4-10)
- RHCE*ceTI
- RHCE*ce48
- RHCE*ceVS.09 or RHCE*ceVS.02
- RHCE*ce.01(1136T) or RHCE*ceTI(105T)
- RHCE*ceVS.03 or RHCE*ce.01−DIVa(2−3,5−9)
Alloimmunization
Antibodies in carriers
Antibody specificity: D (RH1)
Summary: allo-anti-D (last update: May 16, 2020)Detailed information
-
Westhoff CM et al. Transfusion (2010)
- Ab specificity: D (RH1)
- Number (auto- or allo-): 14
- Number listed as allo-:
- Number listed as auto-:
- Number of carriers of the allele assessed: 28 (patients homozygous for RHef00058 or heterozygous with RHef00446)
- DAT:
- Autologuous control:
- Elution:
- Autoadsorption:
- Titer:
- Was anti-LW 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:
- Comment: 13/14 were patients homozygous for RHef00058 or heterozygous with RHef00446, 1 was heterozygous with RHef00672 (differs by 1 silent mutation); study also lists 8 with RHef00442 in trans (no anti-D); most patients had multiple antibodies, see article for details; in Discussion: "Sixteen of 37 (43%) of the pregnant or transfused patients in this report had anti-D", grouping RHef00058 and RHef00672
-
Reid ME et al. Immunohematology (2012)
- 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:
- Autologuous control:
- Elution:
- Autoadsorption:
- Titer:
- Was anti-LW excluded?:
- Other antibodies detected:
- Cross matches (with Ab and RBCs from different partial types):
- Transfusion history:
- Pregnancy history:
- Anti-D Ig history:
- Context: SCD patient
- Hemolytic consequences:
- Comment:
-
Sippert E et al. Blood Transfus (2015)
- Ab specificity: D (RH1)
- Number (auto- or allo-):
- Number listed as allo-: 3
- Number listed as auto-:
- Number of carriers of the allele assessed:
- DAT: ND
- Autologuous control: ND
- Elution: ND
- Autoadsorption: ND
- Titer: ND
- Was anti-LW excluded?: ND
- Other antibodies detected: ND
- Cross matches (with Ab and RBCs from different partial types): ND
- Transfusion history: yes, number and phenotypes ND
- Pregnancy history:
- Anti-D Ig history: ND, probably none
- Context: among 48 SCD patients with RH antibodies despite antigen-matched transfusion protocols
- Hemolytic consequences: 2 of the 13 patients with delayed hemolytic transfusion reactions or decreased survival of transfused RBCs had this allele
- Comment: study does not detail serology for each sample, but mentions performing DAT, autologuous control, eluate studies and adsorption on autologuous RBCs to aid the differenciation of autoantibodies and alloantibodies
-
Westhoff CM et al. Transfusion (2007)
(Table 3)
- Ab specificity: D (RH1)
- Number (auto- or allo-): 3
- Number listed as allo-:
- Number listed as auto-:
- Number of carriers of the allele assessed: ND
- DAT: ND
- Autologuous control: ND
- Elution: ND
- Autoadsorption: ND
- 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: none
- Comment:
-
Daniels G et al. Br J Haematol (2013)
(review)
- 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: one of the 2 most common D variants associated with alloanti-D production in individuals of African descent
-
Noizat-Pirenne F et al. Transfus Clin Biol (2011)
(review)
- 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: frequent descriptions, in individuals of African descent, or compatible with such descent (last update: April 28, 2020)Detailed reports
-
2 samples African American
(aslo included in
20088832 ) - 28/310 (7 hemi or homozygous, 1 heterozygous with RHef00020; 20 could be RHef00442 associated with RHef00058 or, less likely, RHef00313 associated with RHef00056) among 1702 samples tested for the combined presence of RHD c.602G and c.667G (700 Dutch White, 310 South African Black, 319 South African Asians, 197 Curacao Black, 176 Ethiopian Black) South African (Black)
- 1/167 (could be RHef00442 associated with RHef00058 or, less likely, RHef00313 associated with RHef00056) among 1702 samples tested for the combined presence of RHD c.602G and c.667G (700 Dutch White, 310 South African Black, 319 South African Asians, 197 Curacao Black, 176 Ethiopian Black) Ethiopian (Black)
- 1/289 289 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
- 3/21 21 samples referred for anti-D in a D positive individual African American or Hispanic, in the USA population (Table 3)
- 3/12 samples investigated for weak C, VS+, hrB–, HrB– phenotype some were African or Afro-Caribbean
- 1 or 2/10 (1 heterozygous with Rhef00018, 1 sample could be RHef00008 heterozygous with RHef00317 or RHef00313 with RHef00056) individuals with D positive phenotype Bantu, subgroup Teke, Boma from villages in the north of Léfini river
- 56/60 (20/21 donors, 5 hemizygous, 2 homozygous, 1 heterozygous with RHef00602, 5 heterozygous with RHef00452, 7 heterozygous with RHef00442; 36/39 patients, 4 homozygous, 1 heterozygous with RHef00672, 15 heterozygous with RHef00452, 8 heterozygous with RHef00442, 6 hemizygous, 2 heterozygous with RHef00447) among 60 individuals (21 donors, 39 patients) phenotyped as RH:54 and/or submitted for investigation to determine the RH genotype in the USA population (inferred African American)
- 1/205 samples with weak D phenotype African descent in the French population
- 1/163 selected variants included for the development of a genotyping assay mainly in the Dutch population (samples may have been included in other studies)
- 24/118 patients or donors with "diverse Rh phenotypes based on typing discrepancies, the presence of alloantibodies in antigen positive people or the presence of a low prevalence antigen marker" African American
- 38/605 random African American donors or SCD patients African American
- 5 alleles in 226 patients SCD children systematically genotyped in an alloimmunization study in the USA population (Philadelphia)
- 9/316 (2 homo- or hemizygous, 1 heterozygous with RHef00447, 6 heterozygous with RHef00442) 316 (280 D positive and 36 D negative) donors were genotyped African descent (FY:-1,-2) in the French population
- 10/127 the cohort was composed of 77 Tswa from Congo, 36 Biaka from Central African Republic, 14 Mbuti from Democratic Republic of the Congo Pygmoid Central African
- 13/220 the cohort was composed of 164 Teke-Congolese (ethnic groups: 60 Akwa, 52 Mbochi, 52 Kuyu) from Congo, 19 Mandenka from Senegal, 25 Yoruba from Nigeria, 12 Bantu from Kenya Nonpygmoid Central African
- 3/48 among 48 SCD patients with RH antibodies despite antigen-matched transfusion protocols African Brazilian
- 3 heterozygotes 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
- 0.011 allele frequency among 480 African American donors African American (in the USA population)
- 0.021 allele frequency among 140 SCD patients African American (in the USA population)
- 0.0 allele frequency from molecular typing of 101 random samples Dogon Malian
- 0.0 allele frequency from molecular typing of 46 random samples Fulani Malian
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]
- Huang CH et al. Human D(IIIa) erythrocytes: RhD protein is associated with multiple dispersed amino acid variations. Am J Hematol, 1997. [Citation] [RHeference]
- Avent ND et al. The rhesus blood group system: insights from recent advances in molecular biology. Transfus Med Rev, 1999. [Citation] [RHeference]
- Wagner FF et al. The DAU allele cluster of the RHD gene. Blood, 2002. [Citation] [RHeference]
- Westhoff CM et al. A new hybrid RHCE gene (CeNR) is responsible for expression of a novel antigen. Transfusion, 2004. [Citation] [RHeference]
- Chen Q et al. Random survey for RHD alleles among D+ European persons. Transfusion, 2005. [Citation] [RHeference]
- Grootkerk-Tax MG et al. RHD(T201R, F223V) cluster analysis in five different ethnic groups and serologic characterization of a new Ethiopian variant DARE, the DIII type 6, and the RHD(F223V). Transfusion, 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]
- Touinssi M et al. Molecular analysis of inactive and active RHD alleles in native Congolese cohorts. Transfusion, 2009. [Citation] [RHeference]
- Pham BN et al. Heterogeneous molecular background of the weak C, VS+, hr B-, Hr B- phenotype in black persons. Transfusion, 2009. [Citation] [RHeference]
- Flegel WA et al. D variants at the RhD vestibule in the weak D type 4 and Eurasian D clusters. Transfusion, 2009. [Citation] [RHeference]
- Westhoff CM et al. DIIIa and DIII Type 5 are encoded by the same allele and are associated with altered RHCE*ce alleles: clinical implications. Transfusion, 2010. [Citation] [RHeference]
- Noizat-Pirenne F et al. Relevance of RH variants in transfusion of sickle cell patients. Transfus Clin Biol, 2011. [Citation] [RHeference]
- Wagner FF and Flegel WA et al. The Human RhesusBase Online ressource, 2011. — Online ressource — [RHeference]
- Reid ME et al. Molecular background of RH in Bastiaan, the RH:-31,-34 index case, and two novel RHD alleles. Immunohematology, 2012. [Citation] [RHeference]
- Lomas-Francis C et al. DIII Type 7 is likely the original serologically defined DIIIb. Transfusion, 2012. [Citation] [RHeference]
- Reid ME et al. The low-prevalence Rh antigen STEM (RH49) is encoded by two different RHCE*ce818T alleles that are often in cis to RHD*DOL. Transfusion, 2013. [Citation] [RHeference]
- Daniels G et al. Variants of RhD--current testing and clinical consequences. Br J Haematol, 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]
- Granier T et al. A comprehensive survey of both RHD and RHCE allele frequencies in sub-Saharan Africa. Transfusion, 2013. [Citation] [RHeference]
- Chou ST et al. High prevalence of red blood cell alloimmunization in sickle cell disease despite transfusion from Rh-matched minority donors. Blood, 2013. [Citation] [RHeference]
- von Zabern I et al. D category IV: a group of clinically relevant and phylogenetically diverse partial D. Transfusion, 2013. [Citation] [RHeference]
- Kappler-Gratias S et al. Systematic RH genotyping and variant identification in French donors of African origin. Blood Transfus, 2014. [Citation] [RHeference]
- Reid ME et al. Genomic analyses of RH alleles to improve transfusion therapy in patients with sickle cell disease. Blood Cells Mol Dis, 2014. [Citation] [RHeference]
- Sippert E et al. Variant RH alleles and Rh immunisation in patients with sickle cell disease. Blood Transfus, 2015. [Citation] [RHeference]
- Ba A et al. RH diversity in Mali: characterization of a new haplotype RHD*DIVa/RHCE*ceTI(D2). Transfusion, 2015. [Citation] [RHeference]
- Srivastava K et al. The DAU cluster: a comparative analysis of 18 RHD alleles, some forming partial D antigens. Transfusion, 2016. [Citation] [RHeference]
- Stef M et al. RH genotyping by nonspecific quantitative next-generation sequencing. Transfusion, 2020. [Citation] [RHeference]
- Floch A et al. Comment from Rheference Online ressource, 2020. — Online ressource — [RHeference]
Last update: Jan. 8, 2021