Two novel alleles on Fucosyltransferase 2 from northern Thai para-Bombay family and computational prediction on mutation effect

Abstract

Background: Major characteristics of the para-Bombay phenotype are the absence of ABH antigens on red blood cells due to fucosyltransferase 1 (FUT1) gene mutation and the presence of these antigens in body secretions due to the active fucosyltransferase 2 (FUT2) gene. An ABO blood group discrepancy can be identified via serological testing, and additional tests can be performed for confirmation. This study aimed to resolve the ABO discrepancy and report two novel alleles on the FUT2 gene in northern Thai para-Bombay families. Study design and methods: Twelve blood samples were collected from five suspected para-Bombay donors and their families. Nucleotide sequences of ABO, FUT1, and FUT2 were analyzed by polymerase chain reaction-sequence-based typing. Bioinformatics tools were used to predict the effect of suspected novel FUT2 alleles. Results: All samples exhibited normal ABO alleles, concordant with serological test results. FUT1 exhibited three known variants (c.328G>A, c.424C>T, and c.658C>T). Although FUT2 exhibited two known variants (c.357C>T and c.385A>T), two novel alleles were observed. One allele consisted of c.98A>G, c.101T>G, and c.357C>T with predicted normal transferase activity, whereas the other consisted of c.357C>T and c.617T>C with predicted abnormal enzyme activity. Discussion: Two novel alleles in FUT2 were reported among the affected para-Bombay individuals of northern Thai families. The c.617T>C variant caused an amino acid change from valine to alanine at position 206, predicted to be an inactive FUT2 enzyme. Inheritance of this variant with the recessive FUT1 allele may lead to inheritance of the rare Bombay blood group in the progeny.