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 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.
Cherif-Zahar
B
B
INSERM U76, GIP-Institut National de la Transfusion Sanguine, Paris, France.
Raynal
V
V
Gane
P
P
Mattei
M G
MG
Bailly
P
P
Gibbs
B
B
Colin
Y
Y
Cartron
J P
JP
D000595:Amino Acid Sequence; D000743:Anemia, Hemolytic / Q000097:blood / Q000235:genetics*; D015703:Antigens, CD / Q000097:blood / Q000235:genetics; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D004910:Erythrocyte Membrane / Q000737:chemistry; D005260:Female; D016153:Genes, Suppressor / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D012204:Rh-Hr Blood-Group System / Q000097:blood / Q000235:genetics*
D015703:Antigens, CD; D001798:Blood Proteins; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; C498523:RHAG protein, human; D012333:RNA, Messenger; D012204:Rh-Hr Blood-Group System