Journal Article

Identification of two functionally deficient plasma alpha 3-fucosyltransferase (FUT6) alleles

Mollicone, R, Larson, G, Elmgren, A, Oriol, R, Börjeson, C, Fletcher, A

2000

Overview

One Indonesian individual without detectable plasma alpha3-fucosyltransferase activity was identified with three point mutations, 730C>G (L244V), 907C>G (R303G), and 370C>T (P124S), in the coding region of one FUT6 allele. Another individual, expressing weak plasma alpha3-fucosyltransferase activity, had the 907C>G together with the 370C>T mutation, but did not have the 730C>G mutation. PCR-RFLP analyses of complete families confirmed the segregation of these alleles and illustrated the existence and inheritance of the [370C>T; 907C>G] mutated allele in three additional families. Altogether, this allele was found heterozygously in nine Indonesian and two Swedish individuals, all with detectable plasma alpha3-fucosyltransferase activities. The FUT6 allele with the three mutations (370C>T; 730C>G; 907C>G) was identified heterozygously in only two Indonesian individuals, both having the inactivating 739G>A mutation in the other allele and both lacking plasma alpha3-fucosyltransferase activity. Enzyme studies made on transiently transfected COS-7 cells demonstrated that the combination of the 370C>T, 730C>G and 907C>G mutations decreased the V(max) by more than 80%, but caused no obvious change of the apparent K(m) values for GDP-fucose and Gal-N-acetyllactosamine. In comparison, chimeric constructs with the isolated 730C>G or 907C>G mutations decreased the V(max) values by about two thirds and one third, respectively.

• Subject: Alleles / Animals / Cell Line / COS Cells / Female / Fucosyltransferases - blood / Fucosyltransferases - deficiency / Fucosyltransferases - genetics / Humans / Lewis Blood-Group System / Lewis X Antigen - blood / Male / Mutation, Missense - genetics / Oligosaccharides - blood / Pedigree / Polymerase Chain Reaction / Polymorphism, Restriction Fragment Length / Transfection