title: Rh-deficiency of the regulator type caused by splicing mutations in the human RH50 gene.
abstract: The Rh polypeptides and the glycoproteins Rh50, CD47, LW, and glycophorin B, which interact in the red blood cell membrane to form a multisubunit complex, are lacking or are severely reduced in the Rh-deficiency syndrome. We previously reported that in several Rhnull patients the RH50 gene was altered at the coding sequence level, resulting in either a single amino acid substitution or the synthesis of a truncated polypeptide. In the present report, we have detected two mutations in the intronic region of the RH50 gene that identify a new molecular mechanism involved in Rh-deficiency. The first mutation affected the invariant G residue of the 3' acceptor splice-site of intron 6, causing the skipping of the downstream exon and the premature termination of translation. The second mutation occurred at the first base of the 5' donor splice-site of intron 1. Both these mutations were found in homozygote state. RNase protection assays demonstrated that the Rh50 mRNA level was strongly reduced or undetectable in the 3' and 5' splice mutants, respectively. The different mutations affecting the RH50 gene are indicative of an heterogeneous mutational pattern, which further supports the hypothesis that the lack of the Rh50 protein may prevent the assembly or transport of the Rh membrane complex to the red blood cell surface.
authors.affiliation: INSERM U76, Institut National de la Transfusion Sanguine, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Chérif-Zahar
authors.forename: G
authors.initials: G
authors.lastname: Matassi
authors.forename: V
authors.initials: V
authors.lastname: Raynal
authors.forename: P
authors.initials: P
authors.lastname: Gane
authors.forename: J
authors.initials: J
authors.lastname: Delaunay
authors.forename: B
authors.initials: B
authors.lastname: Arrizabalaga
authors.forename: J P
authors.initials: JP
authors.lastname: Cartron
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001692:Biological Transport; D001798:Blood Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D004910:Erythrocyte Membrane / Q000378:metabolism; D005796:Genes; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007438:Introns / Q000235:genetics; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D017354:Point Mutation; D014176:Protein Biosynthesis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012204:Rh-Hr Blood-Group System / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D001798:Blood Proteins; D006023:Glycoproteins; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; C498523:RHAG protein, human; D012333:RNA, Messenger; D012204:Rh-Hr Blood-Group System