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Mutations that diminish expression of Kell surface protein and lead to the K mod RBC phenotype
Author(s) -
Lee Soohee,
Russo David C.W.,
Reid Marion E.,
Redman Colvin M.
Publication year - 2003
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1046/j.1537-2995.2003.00472.x
Subject(s) - mutant , phenotype , exon , mutation , microbiology and biotechnology , biology , gene , point mutation , hek 293 cells , wild type , transfection , mutant protein , genetics
BACKGROUND: K mod is an inherited rare RBC phenotype characterized by weak but detectable expression of high‐incidence Kell antigens. STUDY DESIGN AND METHODS: The 19 exons and the intron‐exon regions of the KEL gene from four unrelated K mod individuals were sequenced and compared to wild‐type KEL . To study the mechanisms by which the mutations result in depression of Kell antigens, mutant and wild‐type Kell proteins were expressed in 293T cells and the amounts of protein present on the cell surface were determined. RESULTS: The following point mutations were identified: K mod −1, homozygous 1208G>A, S363N; K mod −2, heterozygous, 1208G>A, S363N and 2150 A>G, Y677C; K mod −3 (previously classified as KEL:−13), heterozygous 1106T>C, L329P and 1716G>A, W532Stop; K mod −4, heterozygous, 2227G>A, G703R and a silent 1839C>T mutation. In transfected 293T cells, fewer G703R and L329P mutant Kell proteins were transported to the cell surface compared with wild‐type Kell protein, and there was no detectable Y677C mutant Kell protein. Previously, it was shown that that S363N Kell protein was not detected on the cell surface. CONCLUSION: Different point mutations, causing amino acid substitutions and presumably altering protein conformation, inhibit transport of the mutant Kell proteins to the cell surface. The different mutations leading to the K mod phenotype explain why anti‐Ku made by persons with the K mod phenotype are not mutually compatible.