RHD*04.01 - RHD*DIVa
(ISBT table: RHD partial D v5.0)
This entry is an RHD allele.
DIV Type 1.1 (obsolete), DIV type 1, DIV type 1.0, DIV.I, DIVa, DIVa (Bel.) (obsolete), DIVa Type 1, DIVa-2 (obsolete), RHD(L62F,A137V,N152T,D350H), RHD*186G>T,410C>T,455A>C,1048G>C, RHD*186T,410T,455C,1048C, RHD*186T,410T,455C,1048C (DIVa),
Molecular data
Nucleotides:
186G>T; 410C>T; 455A>C; 1048G>C;
Amino acids: L62F; A137V; N152T; D350H;
Hybrid allele encompassing at least one RHCE exon:
no
Comments on the molecular basis:
- initially described without c.410C>T p.A137V
- c.410C>T A137V corrected by family study
- 410C>T corrected by family study
- see also "Additional comments" section on the RhesusBase http://www.rhesusbase.info/RHDDIVa-2.htm
- "original DIVa report missed 410C>T change"
Extracellular position of one or more amino acid substitutions:
Splicing:
Unconventional prediction methods:
Phenotype
Main D phenotype: variable/discrepant (last update: May 4, 2020)Reports by D phenotype
Other RH phenotypes: RH:-2, -3, -8, -23, 30, -32, -50, -56,
Serology with monoclonal anti-D
Antigen Density (Ag/RBC)
More phenotype data
Rhesus Similarity Index
Haplotype
Main CcEe phenotype association: ce (last update: June 20, 2020)ce | Ce | cE | CE | |
---|---|---|---|---|
ce | 1 | 1 | 0 | 0 |
Ce | 0 | 0 | 0 | |
cE | 0 | 0 | ||
CE | 0 |
Reports by CcEe phenotype
Reports by allele association
Alloimmunization
Antibodies in carriers
Antibody specificity: D (RH1)
Summary: probably allo-anti-D (last update: May 16, 2020)Detailed information
-
Wagner FF et al. Transfus Med Hemother (2014)
(RIR n°24)
- Ab specificity: D (RH1)
- Number (auto- or allo-):
- Number listed as allo-: 1
- Number listed as auto-:
- Number of carriers of the allele assessed:
- DAT: negative
- Autologuous control: ND
- Elution: ND
- Autoadsorption: ND
- Titer: 256
- Was anti-LW excluded?: yes
- Other antibodies detected: ND
- Cross matches (with Ab and RBCs from different partial types): ND
- Transfusion history: none
- Pregnancy history:
- Anti-D Ig history: ND, probably none
- Context: ND
- Hemolytic consequences: ND
- Comment:
von Zabern I et al. Transfusion (2013) (Table 2)
-
Wagner FF et al. Transfus Med Hemother (2014)
(RIR n°118)
- Ab specificity: D (RH1)
- Number (auto- or allo-):
- Number listed as allo-: 1
- Number listed as auto-:
- Number of carriers of the allele assessed:
- DAT: positive
- Autologuous control: ND
- Elution: negative
- Autoadsorption: ND
- Titer: 16
- Was anti-LW excluded?: yes
- Other antibodies detected: ND
- Cross matches (with Ab and RBCs from different partial types): ND
- Transfusion history: none
- Pregnancy history:
- Anti-D Ig history: ND, probably none
- Context: ND
- Hemolytic consequences: ND
- Comment:
von Zabern I et al. Transfusion (2013) (Table 2)
-
Noizat-Pirenne F et al. Transfus Clin Biol (2011)
- 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: 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, probable
- Pregnancy history:
- Anti-D Ig history: ND
- Context: among 17 SCD patients with anti-D
- Hemolytic consequences:
- Comment:
-
Aeschlimann J 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:
- 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:
-
Sippert E et al. Blood Transfus (2015)
- Ab specificity: D (RH1)
- Number (auto- or allo-):
- Number listed as allo-: 2
- 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: none 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-): 6
- 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:
-
Chou ST et al. Blood (2013)
(Patient ID 14)
- Ab specificity: D (RH1)
- Number (auto- or allo-): 1 (heterozygous with RHef00452)
- Number listed as allo-:
- 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: none
- Cross matches (with Ab and RBCs from different partial types): ND
- Transfusion history: 181 RBC exposures
- Pregnancy history:
- Anti-D Ig history: ND, probably none
- Context: SCD child
- Hemolytic consequences: none
- Comment: Anti-D not detectable after 1 month
-
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
Daniels G et al. Br J Haematol (2013) (review; Table I)
Antibodies in D negative recipients
Alloimmunization in recipients: expected to be possible, see phenotype data
Reports
Summary: several descriptions, in individuals of African descent, or compatible with such descent (last update: April 28, 2020)Detailed reports
- 1 sample in the French population (sample DIVa (Bel.))
- 6/21 21 samples referred for anti-D in a D positive individual African American or Hispanic, in the USA population (Table 3)
- 1/10 (heterozygous with RHef00020) individuals with D positive phenotype Bantu, subgroup Teke, Kukuya from villages around Djambala city
- 1/45 (prevalence among weak D phenotype) or 1/12672 (phenotypic prevalence in population) 45 patients with weak D phenotype were genotyped in a cohort of 12672 patients from a public hospital Argentinean
- 0/43 (prevalence among weak D phenotype) or 0/5707 (phenotypic prevalence in population) 43 patients with weak D phenotype were genotyped in a cohort of 5707 patients from a private laboratory Argentinean
- 1/205 weak D phenotype African descent, in the French population
- 3/163 selected variants included for the development of a genotyping assay mainly in the Dutch population (samples may have been included in other studies)
- 0/78156 donations, of which 60965 had D positive phenotype. 8 donors with RHef00606 were detected by serologic screening and further characterized by molecular analysis. None of those was RHef00067 in the German population, southwestern Germany
- 8 alleles in 226 patients SCD children systematically genotyped in an alloimmunization study in the USA population (Philadelphia)
- 1/50 (heterozygous with RHef00008) among 50 donors, the majority referred because of ambiguous RH5 antigen typing, found to have RHCE*ceMO (44 with RHef00008, 6 with RHef00442) in the USA population
- 6/316 (2 homo- or hemizygous, 1 heterozygous with RHef00447, 3 with RHef00442) 316 (280 D positive and 36 D negative) donors were genotyped African descent (FY:-1,-2) in the French population
- 0/127 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
- 4/220 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
- 1/360 donors with atypical D phenotype (discrepancies or reactivity weaker than 3+) Brazilian
- 5/48 (samples heterozygous with RHef00452) among 48 SCD patients with RH antibodies despite antigen-matched transfusion protocols African Brazilian
- 1/400 among random blood and bone marrow donors genotyped for RHD In the Brazilian population, Parana state, Southern Brazil
- 1 sample with a D positive phenotype and anti-D Black, in the USA population
- 16/94 donors with discreapancies in D typing Southeast Brazil
- 3 hemizygotes, 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
- highest estimate 1/26087 estimated phenotype frequency among 78156 blood donations of which 60965 had D positive phenotype in the German population, southwestern Germany
- 0.014 allele frequency among 140 SCD patients African American (in the USA population)
- 0.013 allele frequency among 480 African American donors African American, in the USA population
- 0,029 allele frequency from molecular typing of 101 random samples Dogon Malian
Structure mapping
Movement | Mouse Input | Touch Input | ||
---|---|---|---|---|
Rotation | Primary Mouse Button | Single touch | ||
Translation | Middle Mouse Button or Ctrl+Primary | Triple touch | ||
Zoom | Scroll Wheel or Second Mouse Button or Shift+Primary | Pinch (double touch) | ||
Slab | Ctrl+Second | Not Available |
References
- International Society of Blood Transfusion et al. International Society of Blood Transfusion (ISBT) allele table Online ressource, 1935. — Online ressource — [RHeference]
- Rouillac C et al. Transcript analysis of D category phenotypes predicts hybrid Rh D-CE-D proteins associated with alteration of D epitopes. Blood, 1995. [Citation] [RHeference]
- Avent ND et al. Molecular basis of the D variant phenotypes DNU and DII allows localization of critical amino acids required for expression of Rh D epitopes epD3, 4 and 9 to the sixth external domain of the Rh D protein. Br J Haematol, 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]
- Liu W et al. Site-directed mutagenesis of the human D antigen: definition of D epitopes on the sixth external domain of the D protein expressed on K562 cells. Transfusion, 1999. [Citation] [RHeference]
- Wagner FF et al. The DAU allele cluster of the RHD gene. Blood, 2002. [Citation] [RHeference]
- Noizat-Pirenne F et al. Rare RHCE phenotypes in black individuals of Afro-Caribbean origin: identification and transfusion safety. 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]
- Touinssi M et al. Molecular analysis of inactive and active RHD alleles in native Congolese cohorts. 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]
- Wagner FF and Flegel WA et al. The Human RhesusBase Online ressource, 2011. — Online ressource — [RHeference]
- Noizat-Pirenne F et al. Relevance of RH variants in transfusion of sickle cell patients. Transfus Clin Biol, 2011. [Citation] [RHeference]
- Brajovich ME et al. Comprehensive analysis of RHD alleles in Argentineans with variant D phenotypes. Transfusion, 2012. [Citation] [RHeference]
- M E Reid et al. DIVa and DIVa-2 are Encoded by the Same RHD Allele Transfusion, 2012. — Abstract — [RHeference]
- Westhoff CM et al. RHCE*ceMO is frequently in cis to RHD*DAU0 and encodes a hr(S) -, hr(B) -, RH:-61 phenotype in black persons: clinical significance. Transfusion, 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]
- Westhoff CM et al. RHCE*ceTI encodes partial c and partial e and is often in cis to RHD*DIVa. 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]
- Granier T et al. A comprehensive survey of both RHD and RHCE allele frequencies in sub-Saharan Africa. Transfusion, 2013. [Citation] [RHeference]
- Daniels G et al. Variants of RhD--current testing and clinical consequences. Br J Haematol, 2013. [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]
- Wagner FF et al. The Rhesus Site. Transfus Med Hemother, 2014. [Citation] [RHeference]
- Arnoni CP et al. How do we identify RHD variants using a practical molecular approach? Transfusion, 2014. [Citation] [RHeference]
- Kappler-Gratias S et al. Systematic RH genotyping and variant identification in French donors of African origin. Blood Transfus, 2014. [Citation] [RHeference]
- Sippert E et al. Variant RH alleles and Rh immunisation in patients with sickle cell disease. Blood Transfus, 2015. [Citation] [RHeference]
- A C Gaspardi et al. RHD variants in blood donors from Southeast Brazil. Transfusion, 2015. — Abstract — [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]
- Zacarias JM et al. Frequency of RHD variants in Brazilian blood donors from Parana State, Southern Brazil. Transfus Apher Sci, 2016. [Citation] [RHeference]
- Aeschlimann J et al. Four novel silenced RHCE. Transfusion, 2018. [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