CHARACTERIZATION OF THE GENE ENCODING THE HUMAN LW BLOOD-GROUP PROTEIN IN LW(-) PHENOTYPES() AND LW()

The LW blood group is carried by a 42-kD glycoprotein that belongs to the family of intercellular adhesion molecules. The LW gene is organiz ed into three exons spanning an HindIII fragment of approximately 2.65 kb. The exon/intron architecture correlates to the structural domains of the protein and resembles that of other Ig superfamily members exc ept that the signal peptide and the first Ig-like domain are encoded b y the first exon. The 5'UT region (nucleotides -289 to +9) includes po tential binding sites for various transcription factors (Ets, CACC, SP 1, GATA-1, AP2) and exhibited a significant transcriptional activity a fter transfection in the erythroleukemic K562 cells. No obvious abnorm ality of the LW gene, including the 5'UT region, has been detected by sequencing polymerase chain reaction-amplified genomic DNA from RhD+ o r RhD- donors and from an Rh-null variant that lacks the ph and LW pro teins on red blood cells. However, a deletion of 10 bp in exon 1 of th e LW gene was identified in the genome of an LW (a- b-) individual (Bi g) deficient for LW antigens but carrying a normal Rh phenotype. The 1 0-bp deletion generates a premature stop codon and encodes a truncated protein without transmembrane and cytoplasmic domain. No detectable a bnormality of the LW gene or transcript could be detected in another L W (a- b-) individual (Nic), suggesting the heterogeneity of these phen otypes. (C) 1996 by The American Society of Hematology.