Three novel alleles in the Kell blood group system resulting in the Knull phenotype and the first in a Native American

• Published in: Transfusion (Philadelphia, Pa.) Vol. 53; no. 11pt2; pp. 2867 - 2871
• Main Authors: Moulds, Joann M., Persa, Rosemary, Rierson, Darbi, Billingsley, Katrina L., Noumsi, Ghislain T., Hue-Roye, Kim, Reid, Marion E.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.11.2013; Wiley Subscription Services, Inc
• Subjects: Adult; Alleles; Blood; Erythroblastosis, Fetal - genetics; Erythroblastosis, Fetal - immunology; Female; Gene Silencing; Humans; Indians, North American - genetics; Infant, Newborn; Kell Blood-Group System - genetics; Kell Blood-Group System - immunology; Male; Middle Aged; Molecular Sequence Data; Mutation, Missense; Phenotype; Pregnancy
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1111/trf.12205

Background Antibodies to Kell antigens can be clinically important but only limited data are published regarding anti‐Ku. Missense nucleotide changes in KEL account for the numerous Kell antigens, the Kmod phenotype, and even the Knull 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‐Ku in Proband 1, which caused hemolytic disease and anemia of the fetus and newborn, was a mixture of immunoglobulin (Ig)G1 and IgG2 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 Exon 18 (Nucleotide c.1972_1975delG) 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*382C/T; Arg128Stop), a missense change (KEL*244T/C; Cys82Arg), and KEL*578T/C (KEL*01/KEL*02). Direct sequencing of cDNA and cloning showed that the KEL*01 allele had 244C, 382C, 578T and the KEL*02 allele carried 244T, 382T, 578C. Conclusions We report a novel single‐nucleotide deletion, a novel nonsense allele, and a novel missense allele all resulting in the Knull phenotype. The anti‐Ku from Proband 1 was clinically important.