A para-Bombay phenotype due to compound heterozygosity involving a novel FUT1 variant

The para-Bombay phenotype is characterized by the lack of ABH antigens on red blood cells, but ABH substances can be found in saliva. In this study, we report a novel FUT1 allele responsible for a para-Bombay phenotype in a pregnant woman.

ABO, H and Lewis phenotypes and the secretor status were studied in blood and saliva samples. ABO, FUT1 and FUT2 genes were sequenced. Haplotypes were determined by clone sequencing. The structural impact of the new FUT1 variant was assessed using ChimeraX and AlphaFold software.

Serological tests revealed a para-Bombay phenotype. Sequencing studies suggested the presence of the ABO*A1.01 and ABO*O.01.01 reference alleles. The molecular analysis of FUT1 revealed the presence of the FUT1*01W.31 allele and the novel c.521T>C variant responsible for the p.Phe174Ser change. FUT2 study showed the homozygous substitution c.390C>T. The analysis of the AlphaFold model of α2FucT1 predicted that Phe174 is a structural residue located deep inside the protein's hydrophobic core.

We identified the FUT1*01W.31 allele in compound heterozygosity with a novel allele carrying the missense substitution c.521T>C as responsible for the para-Bombay phenotype. In silico studies support that the p.Phe174Ser gives rise to a weak FUT1 variant.