Candidate gene acting as a suppressor of the RH locus in most cases of Rh-deficiency

Abstract

The Rh antigen is a multi-subunit complex composed of Rh polypeptides and associated glycoproteins (Rh50, CD47, LW and glycophorin B); these interact in the red cell membrane and are lacking or severely reduced in Rhnull cells. As a result, individuals with Rhnull suffer chronic haemolytic anaemia known as the Rh-deficiency syndrome. Most frequently, Rhnull phenotypes are caused by homozygosity of an autosomal suppressor gene unlinked to the RH locus (Rhnull regulator or Rhmod types). We have analysed the genes and transcripts encoding Rh, CD47 and Rh50 proteins in five such unrelated Rhnull cases. In all patients, we identified alteration of Rh50--frameshift, nucleotide mutations, or failure of amplification--which correlated with Rhnull phenotype. We propose that mutant alleles of Rh50, which map to chromosome 6p11-21.1, are likely candidates for suppressors of the RH locus accounting for most cases of Rh-deficiency.

The RHD gene is highly detectable in RhD-negative Japanese donors.

“…The candidates for the Rh-related comolecules included the Rh50 glycoprotein, LW glycoprotein, glycophorin B, CD47 glycoprotein, and Duffy glycoprotein (33,34). Among them, Cherif-Zahar et al (35) have proposed the Rh50 glycoprotein as a comolecule common to the RhD and RhCE polypeptides through investigating five Rhnull individuals whose red cells lacked all antigens (D, C/c, and E/e) of the Rh system. In these Rhnull cases, the Rh50 glycoproteins have shown genomic alterations of frameshift, nucleotide mutations, and failure of amplification.…”

Immunochemical Analysis of the Human Erythrocyte Rh Polypeptides

“…The Rh proteins are tightly associated with an ancestrally related glycoprotein component, the Rh glycoprotein (15)(16)(17). Although the involvement of the Rh glycoprotein in Rh antigen expression is not known, it is critical for assembly of the Rh complex, as defects in its structural gene result in the Rh null phenotype (18).…”

Whole-exome sequencing for RH genotyping and alloimmunization risk in children with sickle cell anemia

“…RhAG is important for targeting RhD and RhCE to the erythrocyte membrane, and gene-inactivating mutations in RHAG are responsible for loss of Rh antigen expression (Rh-null). 21 The RHAG V270I (c.808G.A change) variant was previously …”