A KEL gene encoding serine at position 193 of the Kell glycoprotein results in expression of KEL1 antigen.
BACKGROUND
The KEL2/KEL1 (k/K) blood group polymorphism represents 578C>T in the KEL gene and Thr193Met in the Kell glycoprotein. Anti-KEL1 can cause severe hemolytic disease of the fetus and newborn. Molecular genotyping for KEL*1 is routinely used for assessing whether a fetus is at risk. Red blood cells (RBCs) from a KEL:1 blood donor (D1) were found to have abnormal KEL1 expression during evaluation of anti-KEL1 reagents.


METHODS
Kell genotyping methods, including KEL exon 6 direct sequencing, were applied. KEL cDNA from D1 was sequenced. Flow cytometry was used to assess KEL1 and KEL2 RBC expression.


RESULTS
RBCs from the donor, her mother, and an unrelated donor gave weak or negative reactions with some anti-KEL1 reagents. Other Kell-system antigens appeared normal. The three individuals were homozygous for KEL C578 (KEL*2) but heterozygous for a 577A>T transversion, encoding Ser193. They appeared to be KEL*2 homozygotes by routine genotyping methods. Flow cytometry revealed weak KEL1 expression and normal KEL2, similar to that of KEL*2 homozygotes.


CONCLUSIONS
Ser193 in the Kell glycoprotein appears to result in expression of abnormal KEL1, in addition to KEL2. The mutation is not detected by routine Kell genotyping methods and, because of unpredicted KEL1 expression, could lead to a misdiagnosis.
Poole
Joyce
J
Bristol Institute for Transfusion Sciences and International Blood Group Reference Laboratory, Bristol, UK.
Warke
Nicole
N
Hustinx
Hein
H
Taleghani
Behrouz Mansouri
BM
Martin
Peter
P
Finning
Kirstin
K
Crew
Vanja Karamatic
VK
Green
Carole
C
Bromilow
Imelda
I
Daniels
Geoff
G
D000328:Adult; D001483:Base Sequence / Q000235:genetics*; D001782:Blood Donors; D004252:DNA Mutational Analysis / Q000379:methods; D018076:DNA, Complementary / Q000235:genetics; D004899:Erythroblastosis, Fetal / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000235:genetics; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007626:Kell Blood-Group System / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide
D018076:DNA, Complementary; D006023:Glycoproteins; D007626:Kell Blood-Group System