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

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 Rh-null, cells. As a result, individuals with Rh-null suffer chronic haemolytic anaemia known as the Rh-deficiency syndrome. Most frequently, Rh-null phenotypes are caused by homozygosity of an autosomal suppressor gene unlinked to the RH locus (Rh-null regulator or Rh-mod types), We have analysed the genes and transcripts encoding Rh, CD47 and Rh50 proteins in five such unrelated Rh-null, cases. In all patients, we identified alteration of Rh50 - frameshift, nucleotide mutations, or failure of amplification - which correlated with Rh-null 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.