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Three uncommon KEL alleles in one family with unusual K ell phenotypes explain a 35‐year old conundrum
Author(s) -
Karamatic Crew V.,
Poole J.,
Burton N.,
Daniels G.
Publication year - 2014
Publication title -
vox sanguinis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 83
eISSN - 1423-0410
pISSN - 0042-9007
DOI - 10.1111/vox.12094
Subject(s) - allele , biology , genetics , exon , complementary dna , microbiology and biotechnology , null allele , mutation , phenotype , genomic dna , antigen , gene
Background Kell is a complex blood group system comprising 35 antigens. Kell antigens are absent from rare red cells of the K o (null) phenotype and expressed only weakly in the K mod phenotype. Molecular analysis of three uncommon KEL alleles elucidated the obscure pattern of inheritance of Kell antigens in one family. Materials and Methods Standard serological methods were employed. All exons, flanking intronic sequence and introns 15 and 16 of KEL were sequenced from genomic DNA. cDNA was obtained from erythroid cells cultured from progenitor cells isolated from peripheral blood. Results The K mod propositus was heterozygous for two KEL mutations: c.2107G>A, p.Gly703Arg and a synonymous mutation, c.1719C>T, in the codon for p.573Gly. Sequencing of cDNA revealed that c.1719C>T caused skipping of exon 16, resulting in a silent allele. Her KEL:3,−4 brother was heterozygous for KEL*03/04 and c.1719C/T. Conclusion A synonymous mutation caused complete exon skipping, despite being located 16 bases downstream of the 3′ splice site, resulting in a null KEL allele. The combined effects of two mod alleles, one responsible for KEL 3 expression and the other for p.Gly703Arg, were probably responsible for an unexpected KEL :3,−4 phenotype.