THE R(0)(HAR)RH-33 PHENOTYPE RESULTS FROM SUBSTITUTION OF EXON-5 OF THE RHCE GENE BY THE CORRESPONDING EXON OF THE RHD GENE

The highly polymorphic Rh (Rhesus) system is encoded by two homologous genes, one encoding the D polypeptide and the other the CcEe polypept ides. Partial D antigens may be caused by gene rearrangements, deletio ns or point mutations. In this study the molecular basis of R(0)(Har) Rh:33, a Rh phenotype of low frequency, is described. The R(0)(Har) Rh :33 phenotype is characterized by partial expression of D, altered exp ression of e, absence of G and the presence of two antigens of low fre quency: Rh33 and FPTT. Southern blot analysis, RHD typing by PCR and s equence analysis of Rh transcripts revealed that the RHD gene is absen t in subjects with this phenotype. Apart from the expected RHCE transc ripts, a new Rh transcript, RHc(D)(e), was identified in three unrelat ed individuals expressing R(0)(Har) Rh:33. The RHc(D)(e) transcript sh owed the same sequence as the RHce transcript, with the exception of e xon 5, which was substituted by the corresponding exon of the RHD gene . A method for PCR-based genotyping was developed to determine specifi cally the c(D)(e) haplotype. The c(D)(e) PCR proved to be a reliable a lternative method for R(0)(Har) Rh:33 typing.