Erythroid urea transporter deficiency due to novel JKnull alleles.
BACKGROUND
The Kidd blood group antigens Jka and Jkb are encoded by the red blood cell (RBC) urea transporter gene. Homozygosity for silent JK alleles results in the rare Jk(a-b-) phenotype. To date, seven JKnull alleles have been identified, and of these, two are more frequent in the Polynesians and Finns. This study reports the identification of other JKnull alleles in Jk(a-b-) individuals of different ethnic or geographic origins.


METHODS
Nine Jk(a-b-) samples and a sample from a Jk(a-b+) mother of a Jk(a+b-) baby were investigated. Polymerase chain reaction amplification and sequence analysis of the JK gene was performed. Western blotting and urea lysis were used to confirm Jk(a-b-) RBCs.


RESULTS
Four novel alleles were identified: two different nonsense mutations, 202C>T (Gln68Stop) and 723delA (Ile262Stop) were identified on otherwise consensus JK*1 and JK*2 alleles, respectively. A missense mutation, 956C>T (Thr319Met), was identified in a JK*1 allele from an African-American and a JK*2 allele in two people of subcontinental Indian descent. Immunoblotting and urea lysis confirmed absence of JK glycoprotein in RBC membranes from a sample carrying the 956C>T mutation. Other previously described JKnull mutations were found in samples of origins other than in which they were first identified.


CONCLUSIONS
The molecular bases of the Jk(a-b-) phenotype are diverse and this is the first report of JKnull alleles in individuals of African and subcontinental Indian descent. Although rare, these alleles should be taken into consideration when planning genotyping strategies for blood donors and patients.
Wester
Elisabet S
ES
Department of Laboratory Medicine, Division of Hematology and Transfusion Medicine, Lund University and Blood Center, University Hospital, Lund, Sweden.
Johnson
Susan T
ST
Copeland
Tama
T
Malde
Ranjan
R
Lee
Edmond
E
Storry
Jill R
JR
Olsson
Martin L
ML
D000483:Alleles; D001483:Base Sequence; D041905:Erythroid Cells / Q000378:metabolism*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D007667:Kidd Blood-Group System / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000172:deficiency*; D009154:Mutation / Q000235:genetics; D000096982:Urea Transporters
D007667:Kidd Blood-Group System; D026901:Membrane Transport Proteins; D000096982:Urea Transporters