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 chron
ic haemolytic anaemia known as the Rh-deficiency syndrome. Most freque
ntly, Rh-null phenotypes are caused by homozygosity of an autosomal su
ppressor gene unlinked to the RH locus (Rh-null regulator or Rh-mod ty
pes), 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.