A novel variant of the RH antigen led a patient developing hemolytic disease of the fetus and newborn (HDFN), according to a recently published study in Vox Sanguinis.
Red blood cells have molecules on their surface called antigens. However, not all persons have the same antigen on their surface; for example, a person is said to be A-positive when he or she has the A antigen on their surface as well as the Rh antigen.
Mothers who are Rh negative and give birth to Rh positive babies develop antibodies against the Rh antigen, as their immune system recognizes it as foreign. In subsequent pregnancies, these antibodies will cross the placenta and destroy fetal red blood cells, causing HDFN.
Learn more about HDFN causes and risk factors
“We report a novel RHAG blood group allele and show in a study of immediate family members that inheritance of this allele is consistent with a low-prevalence antigen responsible for haemolytic disease of the fetus and newborn (HDFN),” the authors wrote.
The case involved a girl born with classical HDFN symptoms (anemia and jaundice). Serologic testing confirmed the diagnosis of HDFN; however, it did not specify against which antigen the reaction occurred. Extensive genetic testing revealed a mutation in the RHAG gene that led to the expression of a low-prevalence antigen in fetal red blood cells.
The Rh blood group consists of various types of antigens, the most common types being the RHD, RHC, and RHE antigens. The Rh-associated glycoprotein (RHAG) is a vital part of the structure of the Rh antigen. Certain mutations of the gene coding for RHAG can lead to mild anemia and other blood anomalies.
“This case study showed that the presence of the novel variant (RHAG c.140T>C), encoding a p.(Phe47Ser) change in the RhAG glycoprotein, was the apparent cause of incompatibility between maternal plasma and that of red cells from the proband, father and older sibling of the proband,” the authors concluded.
