A new h allele detected in Europe has a missense mutationin alpha(1,2)-fucosyltransferase motif II.
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.
Wagner
T
T
Department of Blood Group Serology and Transfusion Medicine, University of Graz, Graz, Austria.
Vadon
M
M
Staudacher
E
E
Schmarda
A
A
Gassner
C
C
Helmberg
W
W
Lanzer
G
G
Flegel
W A
WA
Wagner
F F
FF
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
D000017:ABO Blood-Group System; D017931:DNA Primers; D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase