(P-IG-10) Bombay Phenotype Identified in an Individual of African Origin

Bombay is a rare phenotype characterized by absence of H, A and B antigens on RBCs and in secretions, and the presence of anti-A, anti-B and anti-H in plasma. It is caused by mutations in the FUT1 and FUT2 genes that lead to non-functional fucosyltransferase enzymes. While the first case was originally described in Bombay (Mumbai) India, the Bombay phenotype has also been found in Southeast Asia and the Middle East, with a reported occurrence of 1 in 10,000. Very few reports exist of Bombay phenotype in an individual of African origin.

Study

Design/Methods:

Case Report:

We investigated a sample from a Group O, D+ 25-year-old African American female with a suspected antibody to a high prevalence antigen. 

Methods:

The ABO, direct antiglobulin test (DAT) and indirect antiglobulin test (IAT) were performed by standard tube methods using untreated, ficin-treated and AET-treated reagent red cells. Sanger sequencing included ABO exons 6 and 7, FUT1 exon 4, FUT2 exon 2, and flanking intron regions.


Results/Findings:

The patient’s serum was strongly reactive with all red cells tested at immediate spin (IS), 37C and IAT by routine saline test tube techniques. The patient’s own cells were negative at all phases of testing and the DAT was negative with Anti-IgG and Anti-C3b,C3d. Antibody reactivity was not diminished when tested against ficin, trypsin, chymotrypsin, papain, pronase and AET (2-aminoethylisothiouronium bromide) treated red cells.  Reactivity decreased from 4+ to 2+ with 0.2M DTT (dithiothreitol), indicating a possible IgM component.  Rare reagent cells lacking high prevalence antigens corresponding to antibodies reactive at IS (Vel-, PP1Pk-, H-) were tested with the patient’s serum.  Two examples of H- selected cells failed to react, consistent with anti-H in her serum. Her red cells type Le(a-b-) and H-.

ABO sequencing detected heterozygous variants c.216delG, c.318C >T, and c.467C >T consistent with an ABO*A1.01 / O.01.09 genotype. FUT1 sequencing revealed a homozygous/hemizygous variant at c.310C >T (p.Gln104Ter) which defines null allele FUT1*01(310T). The change is listed on gnomAD v.4.1.0 with an overall frequency of 0.00003622 (rs780144618). FUT2 sequencing revealed homozygous/hemizygous variants c.204A >G (silent), c.249C >T (silent), c.451G >A (p.154Ter), c.772G >A (p.258Ser), c.993A >G (silent) which constitute null allele FUT2*01N.02.
 

Conclusions:

Although the patient is predicted to be Group A, the presence of non-functional FUT1 and FUT2 alleles results in the loss of H and A antigen on RBCs and secretions resulting in an O_h blood type in a patient with alloanti-H. 

FUT1*01(310T) has been previously described in compound heterozygosity with c.496G >T in a patient and his 2 siblings of Irish descent (2015 Vox Sang 109(S1), P-566). Interestingly, here, the c.310C >T was detected in an individual of African descent highlighting the diversity of the Bombay phenotype.