MOLECULAR DEFECTS OF THE RHCE GENE IN RH-DEFICIENT INDIVIDUALS OF THEAMORPH TYPE

The deficiency of Rh proteins on the red blood cells from individuals of the Rh-null amorph type may be the result of homozygosity for a sil ent allele at the RH locus, This phenotype is also associated with the lack or reduced expression of glycoproteins (Rh50, CD47, LW, and glyc ophorin B), which interact with Rh polypeptides to form the multisubun it Rh membrane complex. In this study, we describe two molecular alter ations affecting the RHCE gene in two unrelated Rh-null amorph individ uals bearing Rh50 and CD47 normal transcripts. The first type of mutat ion, located at the donor splice-site in intron 4, induced the activat ion of two cryptic splice-sites within this intron and one such site i n exon 4 that all generated aberrant transcripts. The second type of m utation affected the coding region and introduced a frameshift and a p remature stop codon resulting in a shorter predicted protein (398 v417 residues), including a completely different C-terminus of 76 amino ac ids. This suggests that protein folding and/or protein-protein interac tion mediated by the C-terminal domain of the ph proteins may play a r ole in the routing and/or stability of the Rh membrane complex. (C) 19 98 by The American Society of Hematology.