RESUMO
BACKGROUND: Rh is one of the most important blood group systems in transfusion medicine. The two homologous genes RHD and RHCE are located on chromosome 1p36.11 and encode for RhD and RhCE proteins, respectively. Complex genetic polymorphisms result in a variety of antigenic expression of D, C, E, c, and e. Here, we describe a case of a young female with D-- who developed anti-Rh17 secondary to blood transfusion and had signs of haemolytic disease of the fetus and fetal death in five consecutive pregnancies. CASE DESCRIPTION: EDTA-whole blood samples were collected from the patient, husband and eight siblings for blood grouping, phenotyping, and red cell antibody screening. Extracted DNA was genotyped by SNP-microarray and massively parallel sequencing (MPS) with targeted blood group exome sequencing. Copy number variation analysis was performed to identify structural variants in the RHD and RHCE. Routine phenotyping showed all family members were D+. The patient's red blood cells were C-E-c-e-, Rh17- and Rh46- and had anti-Rh17 and anti-e antibodies. MPS showed the patient carried a wildtype RHD sequence and homozygous for RHCE (1)-D (2-9)-CE (10) hybrid gene predicted to express a D-- phenotype. CONCLUSIONS: Our patient had a rare D-- phenotype and confirmed to have RHCE/RHD hybrid gene with replacement of 2-9 exons of RHCE by RHD sequences. Unfortunately, our patient developed anti-Rh17 and anti-e antibodies due to blood transfusion and suffered fetal demise in her very first pregnancy. The adverse outcomes could have been prevented by active prenatal management.
