title: A new h allele detected in Europe has a missense mutationin alpha(1,2)-fucosyltransferase motif II.
abstract: BACKGROUND
  The FUT1 gene encodes an alpha(1,2)-fucosyltransferase (H transferase), which determines the blood group H. Nonfunctional alleles of this gene, called h alleles and carrying loss-of-function mutations, are observed in the exceedingly rare Bombay phenotype. Twenty-three distinct h alleles have been characterized at the molecular level in various populations. The FUT2 (SE) gene is highly homologous to FUT1 (H:).
  
  
  METHODS
  The FUT1 gene of an Austrian proband with the Bombay phenotype was characterized by nucleotide sequencing of the full-length coding sequence. A PCR method using sequence-specific primers for FUT2 genotyping in whites was developed. The plasma alpha(1,2)-fucosyltransferase activity was determined. The distribution of the mutations underlying 24 h alleles and 7 se alleles was analyzed.
  
  
  RESULTS
  The proband carried a new h allele. Two nucleotide changes, G785A and C786A, in codon 262 of the FUT1 gene resulted in the replacement of serine by lysine. No alpha(1,2)-fucosyltransferase activity was detected in the proband's plasma. The proband was homozygous for the seG428A allele. Six of 17 missense mutations in nonfunctional h and se alleles occurred in highly conserved fucosyltransferase motifs. No loss-of-function mutation was observed in the aminoterminal section encompassing the transmembraneous helix.
  
  
  CONCLUSIONS
  The missense mutation S262K in the FUT1 gene caused the loss of H transferase activity. The analysis of the distribution of mutations in nonfunctional FUT1 and FUT2 genes can point to functionally important domains in the H transferase.
authors.affiliation: Department of Blood Group Serology and Transfusion Medicine, University of Graz, Graz, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Wagner
authors.forename: M
authors.initials: M
authors.lastname: Vadon
authors.forename: E
authors.initials: E
authors.lastname: Staudacher
authors.forename: A
authors.initials: A
authors.lastname: Schmarda
authors.forename: C
authors.initials: C
authors.lastname: Gassner
authors.forename: W
authors.initials: W
authors.lastname: Helmberg
authors.forename: G
authors.initials: G
authors.lastname: Lanzer
authors.forename: W A
authors.initials: WA
authors.lastname: Flegel
authors.forename: F F
authors.initials: FF
authors.lastname: Wagner
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics; D000483:Alleles; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence / Q000235:genetics; D001317:Austria; D001483:Base Sequence / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D017931:DNA Primers; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D005647:Fucosyltransferases / Q000097:blood / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010641:Phenotype; D016133:Polymerase Chain Reaction; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D000017:ABO Blood-Group System; D017931:DNA Primers; D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase