Hemolytic disease of the newborn due to anti-Jra from a Chinese mother with one novel and one classic heterozygous mutation

Objective: Investigation of a Jr(a-) family samples, identification of the mutant and assessment of the differences of Jr antigen density of the Jr(a-) family members, random adult and newborn individuals' RBCs.Background: The anti-Jra antibody is generated when a Jr(a-) individual pregnant or transfused with Jr(a+) blood unit, which can lead to mild-to-moderate hemolytic disease of the foetus and newborn (HDFN) or hemolytic transfusion reaction (HTR). Several mutations had been identified. The anti-Jra caused HDFN is not rare in East Asia, but due to the lack of antibody and molecular background, it is likely to lead missed detection.Methods and Materials: One G4P1 woman had been detected as IAT positive during prenatal examination. Suspected as anti-Jr(a) after the laboratory serological testing, the maternal sample was further assessed by molecular analysis. The antigen density was detected by flow cytometry after reacting with anti-Jr(a) serum in family members and the normal individuals.Results: One novel frameshift mutation c.717delC and one previously identified mutation c.706C > T in ABCG2 was identified on proband. The infant haemoglobin(Hb) and bilirubin increased significantly after exchange transfusion and the severe HDFN was relieved. Flow cytometry results showed that the Jr(a) antigens on adult RBCs were significantly less than those on the infant.Conclusion: The c.717delC mutation can lead to the shortening of protein ABCG2 in the site of p.Leu307Stop, result in the loss of Jr(a) antigen. The difference in antigen density between adult and infant RBCs may be a possible reason that leads to severe HDFN but not transfusion reaction. Breastfeeding may lead to slower recovery from HDFN.