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Three novel alleles in the K ell blood group system resulting in the K null phenotype and the first in a N ative A merican
Author(s) -
Moulds Joann M.,
Persa Rosemary,
Rierson Darbi,
Billingsley Katrina L.,
Noumsi Ghislain T.,
HueRoye Kim,
Reid Marion E.
Publication year - 2013
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12205
Subject(s) - missense mutation , microbiology and biotechnology , null allele , allele , biology , proband , frameshift mutation , genetics , nonsense mutation , exon , phenotype , mutation , gene
Background Antibodies to K ell antigens can be clinically important but only limited data are published regarding anti‐ K u. Missense nucleotide changes in KEL account for the numerous K ell antigens, the K mod phenotype, and even the K null phenotype. Study Design and Methods DNA and RNA were extracted from white blood cells and polymerase chain reaction–based assays, cloning, and sequencing were done using standard protocols. Results The anti‐ K u in P roband 1, which caused hemolytic disease and anemia of the fetus and newborn, was a mixture of immunoglobulin ( Ig ) G 1 and IgG 2 and gave macrophage indexes ranging from 47.8 to 59.3 (>20 is clinically significant) in a monocyte monolayer assay. The proband, her daughter, and compatible sister had a heterozygous deletion of a G in E xon 18 ( N ucleotide c.1972_1975del G ) in a KEL*02 allele causing a frameshift. The mechanism for silencing of the other KE*02 allele was undetermined. Proband 2 was heterozygous for a nonsense change ( KEL * 382 C / T ; A rg128 S top), a missense change ( KEL * 244 T / C ; C ys82 A rg), and KEL * 578 T / C ( KEL*01/KEL*02 ). Direct sequencing of cDNA and cloning showed that the KEL*01 allele had 244 C , 382 C , 578 T and the KEL*02 allele carried 244 T , 382 T , 578 C . Conclusions We report a novel single‐nucleotide deletion, a novel nonsense allele, and a novel missense allele all resulting in the K null phenotype. The anti‐ K u from P roband 1 was clinically important.