A CASE OF A WEAK D-PRIMIPAROUS WOMAN CARRING A NOVEL VARIANT RHD GENE

Abstract

Background: To prevent anti-D alloimmunization by D-positive RBCs derived from an infant or newborn, the administration of Rh human-immunoglobulin (RhIG) to D-negative women without anti-D antibody is recommended during pregnancy or at delivery. However, there is no guidance for pregnant woman with the weak D phenotype in Japan.
Case and Results: A primigravid woman was admitted to our hospital at 34 week's gestation. Her RhD typed as weak D because her RBCs were not agglutinated by the immediate spin method but were positive by the indirect antiglobulin test using a commercial anti-D reagent. RhIG was not administered to the woman during pregnancy or at delivery despite her first baby being D-positive. However, anti-D alloantibodies were not detected in her sera during pregnancy or at delivery. Her RHD gene was suspected to be D variant and analyzed. According to the sequencing results of the RHD gDNA and RHD cDNA derived from peripheral reticulocytes, the pregnant woman had a novel RHD gene with A>G mutation at the splicing acceptor site of intron 4. This intronic mutation may cause alternative splicing as a consequence of its generating a unique transcript with an 87 base insertion.
Conclusion: We experienced a case of a weak D primiparous woman in whom RhIG was not administered during the perinatal period or at delivery. Her first baby was D-positive. However, anti-D alloimmunization was not induced. She has a novel RHD(IVS4-2A>G) with A>G mutation at the splicing accepter site of intron 4. It was considered that abnormal splicing may have caused the weak D with a 29-amino acid insertion.