Inheritance of the Rh_null and Rh_mod Phenotypes

There are two genetic mechanisms that give rise to the Rh_null phenotype: regulator and amorphic. In the regulator-type Rh_null a mutation occurs in the RHAG gene, resulting in no expression of the RhAG protein and no RhD or RhCE protein expression on the red cells, despite normal inheritance of RHD and RHCE genes. These individuals can pass normal Rh genes to their offspring. In the amorphic-type Rh_null, there is a mutation in the RHCE gene inherited from each parent and the common deletion of the RHD gene found in most individuals. These individuals have inherited a normal RHAG gene. Rh_null individuals of either type lack the high prevalence antigen LW and FY5, an antigen in the Duffy blood group system. Antigens found on glycophorin B (S, s, and U) may also be depressed.

Individuals of the Rh_mod phenotype have partial suppression of the RH gene expression caused by mutations in the RHAG gene. The red cells of these individuals possess other blood group antigens, but may show weakened expression of Rh and LW antigens and depressed expression of S, s, and U antigens. These individuals may exhibit features similar to Rh_null syndrome, but their symptoms are less severe and rarely problematic clinically.