A combination of the effects of rare genotypes at the XK and KEL blood group loci results in absence of Kell system antigens from the red blood cells

Abstract

The 22 antigens of the Kell blood group system are located on a red blood cell (RBC) membrane glycoprotein that shows sequence homology with a family of metalloendopeptidases. Expression of the Kell system antigens is partially governed by XK, an X-linked gene that encodes the Kx protein; absence of Kx results in reduced Kell antigen expression. Almost total absence of Kell antigens from the RBCs of a German man with no symptoms of neuroacanthocytosis could not be due to the Kell- null phenotype, Ko, because his RBCs had very weak expression of Kx antigen and his three children were Kp(a + b+). Kell antigens were normal on the RBCs of his son but weak on those of his two daughters. An Nla III restriction fragment-length polymorphism within the KEL gene showed the Kpa/Kpa genotype in the propositus. Sequencing of his XK gene showed a single base change within the donor splice consensus sequence of intron 2. A BsaAl restriction fragment-length polymorphism showed the mutation in both of his daughters but not in his son. The extreme depression of the Kell antigens of the propositus must be due to a combination of effects, ie, homozygosity for Kpa and deficiency of Kx protein, each of which is capable of causing some degree of weakening of Kell antigens.

McLeod phenotype associated with a XK missense mutation without hematologic, neuromuscular, or cerebral involvement

“…17 The vast majority of disease-causing XK mutations, however, comprised deletions, nonsense, or splice-site mutations predicting absent or truncated XK protein devoid of the Kell protein binding site. 3,4,9,[15][16][17][30][31][32] RBC protein Western blotting demonstrated absent RBC membrane-bound XK protein and XK/Kell complex. However, the wild-type XK-Western blot was not very strong under reducing conditions, most probably because reduced XK aggregates.…”

Molecular Basis of Kell Blood Group Phenotypes

“…For example, depression of most Kell antigens can occur in some KEL3,-4 individuals but is most noticeable in KEL3,-4/Ko heterogygotes [12]. Recently it has been shown that a person with the KEL3 allele expressed almost no Kell antigens and this severe depression was due to a point mutation in a splice consensus sequence of XK, which would lead to absence of XK on the red cell membrane (McLeod phenotype) [43].…”

The value of DNA analysis for antigens of the Kell and Kx blood group systems

“…5,46 In one case, the mutation occurs in an intron, five nucleotides downstream from the splice site, resulting in alternative splicing and a low level of normal splicing. 33,47 In this case, although a reduced level of normal XK is expected to be produced, Kx antigen was not detected on RBCs. Table 2).…”