GBGT1 is allelically diverse but dispensable in humans and naturally occurring anti-FORS1 shows an ABO-restricted pattern

• BACKGROUND: The FORS histo-blood group system was described in 2013 and much remains to be investigated regarding its genetic and immunohematologic characteristics, as well as its clinical importance. While presence of the c.887G>A-mutated GBGT1 gene, which results in FORS1 glycosphingolipid expression on human red blood cells (RBCs), is rare in the populations tested so far, naturally occurring anti-FORS1 in plasma appears common. STUDY DESIGN AND METHODS: The Erythrogene database was utilized to probe genetic variation in GBGT1 among 2504 individuals in the 1000 Genomes Project. We screened 1108 Swedish blood donors for three principally important single-nucleotide polymorphisms (c.363C>A, c.886C>T, and c.887G>A) and selected samples were analyzed further. Screening for naturally occurring anti-FORS1 in plasma from 100 donors was performed using antigen-positive RBCs. RESULTS: We identified 68 GBGT1 alleles, of which three were previously listed blood group alleles. Eight potential null alleles were observed, based on three different nonsense mutations. Four healthy donors were found homozygous for c.363C>A, which truncates the GBGT1-encoded Fs synthase prematurely. This is the first description of human knock-outs for GBGT1. The c.886C>T mutation that alters the same codon (p.Arg296Trp) changed by c.887G>A (p.Arg296Gln) was overexpressed to investigate if it induces the FORS1+ phenotype. However, c.886C>T did not result in synthesis of FORS1. We detected anti-FORS1 in 10% of all donors tested but none in the A1 or A1B groups. CONCLUSION: We have extended the knowledge of GBGT1 variants, allele frequencies, and the characteristics of naturally occurring antibodies in our newest carbohydrate blood group system, FORS. The finding of c.363C>A-homozygous donors indicates that GBGT1 is dispensable.

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)

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