Evidence for a separate genetic origin of the partial D phenotype DBT in a Japanese family

BACKGROUND: In a Moroccan family, the partial D phenotype DBT is defined by an RHD-CE-D gene in which exons 5 to 7 of RHD were replaced by those of RHCE. In this study, the molecular basis and inheritance of DBT in a Japanese family are described. STUDY DESIGN AND METHODS: A Japanese proposita exhibiting the DBT phenotype was analyzed by serologic methods and molecular techniques. The RH transcripts of the proposita were sequenced and compared with those of normal donors. The inheritance and structure of the RH genes in the family were determined by Southern blot analysis and exon-specific polymerase chain reaction. RESULTS: The proposita typed weak D and C+c+E+e+Rh:32. Family data indicated a cotransmission of Rh32 with DBT and a linkage of C and e with DBT. Southern blot testing of the proposita's genomic DNA indicated a partial and a total absence of RHD on the respective homologous chromosomes. Sequencing of her cDNA showed expression of Ce, cE, and RHD-CE-D transcripts but not D. The RHD-CE-D hybrid was characterized by a conversion of five RHD exons into RHCE exons (exons 5-9). The 5' and 3' breakpoints in the fusion gene were localized to the intron 4/exon 5 region and intron 9. CONCLUSION: The new RHD-CE-D gene defines a separate genetic origin of DBT in the Japanese family The proximal sequence encoded by RHD exon 4 and RHCE exon 5, together with the distal RHCE sequence, may involve the cotransmission of Rh32 and DBT, which behave as codominant and recessive characters, respectively.