Molecular analysis of plasma α1,3-fucosyltransferase deficiency and development of the methods for its genotyping

Four patients with mental illness were found to be deficient in plasma α1,3-fucosyltransferase for the first time in Japan [Exp Clin Immunogenet 1999;16:125-130]. Complete sequencing of FUT6 genes in these individuals revealed the presence of two point mutations, i.e., G739 to A (Glu → 247 to Lys) and C945 to A (Tyr → 315 to stop). In addition to two reported alleles having G739 to A (pf1) and G739 to A and C945 to A (pf3), a new mutated allele having C945 to A (pf2) was found to be present and all the individuals who lack α1,3-fucosyltransferase activity in plasma were found to possess pf genes homozygously (pf/pf). In order to detect such lethal mutations in FUT6 genes easily, PCR-RFLP methods have also been developed and applied for the screening of FUT6 deficiency in a large number of samples which resulted in the demonstration of three additional FUT6-deficient individuals. The absence of α1,3-fucosylated molecules on α₁-acid glycoprotein in plasma from all the 7 individuals was confirmed to result from the plasma α1,3-fucosyltransferase deficiency.