Rh‐null phenotype caused by a complete RHAG deletion

A variant RhAG protein encoded by the RHAG*572A allele causes serological weak D expression while maintaining normal RhCE phenotypes

“…The donor had a serological weak D but a normal C + c‐ E– e + phenotype rather than the Rh null or Rh mod phenotype, and further in vitro expression studies also confirmed that RHAG*572A allele only affected the RhD antigen and not the RhCE antigens. Thus, unlike previously reported RHAG mutations that affected both RhD and RhCE antigens, RHAG*572A resulting in Arg191Gln only affects the RhD antigen. This Arg191Gln mutation does not affect the assembly with the RhCcEe polypeptides.…”

“…Biochemical data have suggested that the most likely in vivo subunit configuration of Rh core complex is RhD‐RhAG 2 and RhCcEe‐RhAG 2. Absence or weakened expression of RhAG, which is caused by the homozygous inactivating mutations or some missense mutations of the RHAG gene, was shown responsible for the complete absence (regulator Rh null ) or severe reduction (Rh mod ) of both RhD and RhCE antigens by complete or partial failure of the assembly of the Rh core complex. Interestingly, the Arg191 is highly conserved among the three human ammonium transporters RhCG, RhBG, and RhAG, and it is also present in a conserved region (LYRR) in all Rh, Amt, and MEP proteins .…”

“…The RhAG antigen is essential for the normal expression of RhD and RhCE antigens on the surface of the red blood cell (RBC) membrane . Mutations of the RHAG gene were reported to result in complete absence (Rh null phenotype) or severe reduction (Rh mod phenotype) of the expression of Rh antigens on the RBC membrane. In addition, ankyrin 1 was recognized as a structural adaptor protein that links membrane proteins to the cytoskeleton and mutations in the ANK1 gene were reported to result in reduced expression of Rh polypeptides …”

First report of Rhnull individuals in the Indian population and characterization of the underlying molecular mechanisms

“…In our study, the propositus in Family 1 did not express RhAG protein due to the homozygous deletion of the whole RHAG gene, thereby impairing the membrane expression of Rh proteins. Whole deletion of the RHAG gene in an Rh null individual was recently reported in a transfused, Caucasian female patient with gynecologic neoplasia (Table S1) . Additional molecular analyses will be required to establish whether the deletion found in this patient and that involved in our family members are the same.…”

“…Whole deletion of the RHAG gene in an Rh null individual was recently reported in a transfused, Caucasian female patient with gynecologic neoplasia (Table S1). 22 Additional molecular analyses will be required to establish whether the deletion found in this patient and that involved in our family members are the same.…”