Identification of a missense mutation (G329A; Arg(110) -> Gln) in the human FUT7 gene

The human FUT7 gene codes for the alpha1,3-fucosyltransferase VII (Fue-TVII ), which is involved in the biosynthesis of the sialyl Lewis x (SLe(X)) epi tope on human leukocytes. The FUT7 gene has so far been considered to be mo nomorphic. Neutrophils isolated from patients with ulcerative colitis were examined for apparent alterations in protein glycosylation patterns by West ern blot analysis using monoclonal antibodies directed against SLe(X) and S Le(X)-related epitopes. One individual showed lower levels of SLe(X) expres sion and an elevated expression of CD65s compared to controls. The coding r egions of the FUT7 gene from this individual were cloned, and a G329A point mutation (Arg(110) --> Gln) was found in one allele, whereas the other FUT 7 allele was wild type. No Fuc-TVII enzyme activity was detected in COS-7 c ells transiently transfected with the mutated FUT7 construct. The FUT7 Arg( 110) is conserved in all previously cloned vertebrate alpha1,3-fucosyltrans ferases. Polymerase chain reaction followed by restriction enzyme cleavage was used to screen 364 unselected Caucasians for the G329A mutation, and a frequency of less than or equal to1% for this mutation was found (3 heteroz ygotes). Genetic characterization of the family members of one of the addit ional heterozygotes identified one individual carrying the G329A mutation i n both FUT7 alleles. Peripheral blood neutrophils of this homozygously muta ted individual showed a lowered expression of SLe(X) and an elevated expres sion of CD65s when analyzed by Western blot and flow cytometry. The homozyg ous individual was diagnosed with ulcer disease, non-insulin-dependent diab etes, osteoporosis, spondyloarthrosis, and Sjogren's syndrome but had no hi story of recurrent bacterial infections or leukocytosis.