Novel RHD gene variant resulting in the abolition of the stop codon. RHD(X418Q)

A number of RHD alleles associated with qualitative or quantitative D antigen variants are reported. Most Rhesus D negatives are due to deletion of the RHD gene. In apparently D neg individuals extremely low levels of D antigen may remain undetected by any routine typing method. D variants detectable by the more sensitive adsorption/elution tests only are known as Del for elution and have also caused the generation of anti-D. Here we describe a novel RHD allele identified in a newborn baby showing a Rhesus D negative phenotype by routine blood grouping.Serologic Rh typing was performed by standard gel card matrix techniques. A direct antiglobulin test (DAT) of the newborn was performed. Molecular genetic analysis included sequencing of the RHD gene. Standard serology showed negative reactions for the presence of D antigen and neonatal cord blood typing revealed a negativ DAT. DNA analysis identified the disruption of the stop codon in exon 10 of the RHD gene. The translation of a protein with 26 additional amino acid residues at the C-terminal is predicted. The novel mutation results in the abolition of the translational stop and elongation of the amino acid sequence in the intracellular domain of the Rh D protein. The gene variant may be responsible for a grossly reduced translation or in a lack of Rhesus D protein expression. The presence of a Del variant, susceptible to anti-D alloimmunization following transfusion or pregnancy may not be excluded.