Identification of a novel Bw allele with c.810C > G missense variation in a Cambodian‐origin family

As of the 38th ISBT Congress in Barcelona in 2024, 47 blood group systems on erythrocytes have been discovered. The ABO system is the most important blood group system in transfusion and transplantation medicine. In addition to the normal A, B, O, and AB phenotypes, there are several ABO subgroups with reduced antigen expression. Gene sequence variation associated with subgroup alleles includes nucleotide insertion, deletion, substitution, and gene recombination. Although more than 200 ABO alleles have been discovered, as far as we know, there are still many new alleles being discovered in the current genomic era.1 Here, we describe a novel B allele related to weak B antigen in a Chinese-Cambodian family. The blood samples including the proband and her family members were collected with informed consent. The ABH blood group was tested for multiple monoclonal and human antibodies and standard cells. The full coding sequence, as well as flanking intronic regions, 5′ untranslated region, and the 5.8 kb region in intron 1 of the ABO gene was amplified and Sanger sequenced by our previous report.2 The haploid sequence of the ABO gene was further analyzed using single-strand amplification with allele-specific primer and sequencing according to our previous method.2 The proband was a 2-year-old girl from a Chinese-Cambodian family who presented at the hospital with symptoms of an upper respiratory infection and underwent routine blood group typing. Blood group serology revealed that her red blood cells expressed normal A and weak B antigens, and an unexpected anti-B was present in her serum. Family investigation revealed that her weak B antigen was inherited from her Cambodian mother (Table 1). Direct sequencing revealed nine heterozygous variants in the ABO coding region of the proband, including c.467C/T, seven ABO*B.01-specific variants, and a new c.810C/G variant. Haploid sequencing revealed a new variant of c.810C > G on the ABO*B.01 allele, which was heterozygous, and an ABO*A1.02 allele. The proband's mother had the same variant B(c.810C > G) allele (Table 1). The c.810C > G variant causes an amino acid change from aromatic phenylalanine to aliphatic leucine at residue 270 (p.Phe270Leu). The variant is predicted to be possibly damaging with a score of 0.943 (sensitivity 0.80 and specificity 0.95) to alpha-1,3-galactosyltransferase (B glycosyltransferase) using an online protein function prediction software, PolyPhen-2.3 This variant has previously been reported in a blood donor of Thai origin presenting with a similar phenotype.4 Two other SNPs have been registered on the c.810 position of the ABO gene in the dbSNP database, including c.810delC (rs1564303826) and c.810C > T (rs782473555). According to our previous ABO gene sequencing study in the Chinese population, no c.810C > G variant was found in 417 random volunteers5 and more samples (data not published), indicating that the frequency of the B(c.810C > G) allele is relatively low in China and may be mainly prevalent in the Southeast Asian population. In conclusion, one novel Bw allele with c.810C > G variation on the ABO*B.01 allele was identified and submitted in GenBank with accession number PQ358374, which was responsible for the weak B antigen expression.