title: Identification of two functionally deficient plasma alpha 3-fucosyltransferase (FUT6) alleles.
abstract: 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.
authors: Institute of Laboratory Medicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
authors: A
authors: A
authors: Elmgren
authors: C
authors: C
authors: Börjeson
authors: R
authors: R
authors: Mollicone
authors: R
authors: R
authors: Oriol
authors: A
authors: A
authors: Fletcher
authors: G
authors: G
authors: Larson
mesh_terms: D000483:Alleles; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D005260:Female; D005647:Fucosyltransferases / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen / Q000097:blood; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D009844:Oligosaccharides / Q000097:blood; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D000080506:Sialyl Lewis X Antigen; D014162:Transfection
chemical_list: D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase