K. Mcmanus et al., An amino acid substitution in the putative second extracellular loop of RBC band 3 accounts for the Froese blood group polymorphism, TRANSFUSION, 40(10), 2000, pp. 1246-1249
BACKGROUND: The low incidence RBC antigen Fr-a has been excluded from 17 of
the 25 established blood group systems. Previous genetic analysis assigned
the gene controlling Fr-a expression to the same chromosomal region as the
solute carrier family 4, anion exchanger member 1 gene (SLC4A1). Because S
LC4A1 encodes RBC band 3 and controls the expression of Diego blood group s
ystem antigens, the possible relationship of Fr-a to the Diego blood group
system was investigated by molecular analysis of SLC4A1.
STUDY DESIGN AND METHODS: Blood samples were obtained from the members of t
wo unrelated Mennonite kindreds segregating for Fra. DNA was extracted, amp
lified by PCR using intronic primer sets flanking exons 11-20 of SLC4A1, an
d screened by single-strand conformation polymorphism (SSCP) analysis. Thos
e exons displaying SSCPs were subjected to DNA sequence analysis.
RESULTS: An exon 13 SSCP mobility shift was observed in the DNA from all Fr
(a+) persons that was not seen in the DNA from Fr(a-) family members or con
trol subjects. Linkage between the exon 13 SSCP and Fa was established, wit
h peak lods = 3.62 at theta = 0.00 for combined paternal and maternal meios
es. DNA sequencing revealed a GAG --> AAG mutation that underlies a Glu480L
ys substitution in RBC band 3.
CONCLUSIONS: A point mutation in exon 13 of SLC4A1 accounting for a Glu480L
ys substitution in band 3 controls Fr-a expression. On the basis of these o
ur results, the International Society of Blood Transfusion Working Party on
Terminology for Red Cell Surface Antigens has assigned Fr-a to the Diego b
lood group system, with the designation D120.