Molecular and Family Analyses of a Novel RHD1058G>C Allele in a Chinese RhD Population

Background: Rh(D) phenotype in a sample from a 19-year-old female patient showed weak positivity (1+). A follow-up sample was requested to further define the Rh(D) phenotype, her Rh(D) phenotype was tested by using another reagent, Rh(D) phenotype still showed weak reactivity (1+), RhCcEe phenotype was Ccee. Methods: Seven samples from the family members of the proposita were received. The RhDCcEe phenotypes were typed by the micro-column gel card and the unexpected antibodies were assayed by indirect anti- human globulin test (IAT). Genomic DNA was extracted from the blood sample and the novel RHD1058G>C allele was detected through an established sequence-specific primer PCR (PCR-SSP), RHD exons 1 - 10 were sequenced afterward by exon-specific amplification. The distribution of RHD1058G>C allele and RHD weak positive phenotype were investigated in the pedigrees. Results: The unexpected antibodies all were negative in the family members. The novel RHD1058G>C allele was found in the proposita, her father, and grandfather. Five family members were detected serologically with the common Rh(D)-positive phenotypes either as homozygote of RHD/RHD or heterozygote of RHD/RHd. Two family members were detected as weak D phenotypes in accordance with the genotyping results by PCR-SSP, and both of them have a (DCe)-Ce-1058 haplotype and a dce haplotype. One member, her father, was tested common Rh( D)-positive with (DCe)-Ce-1058 haplotype and a Dce haplotype. Conclusions: These data allow us to describe the characteristics of the weak D phenotype with a novel c. RHD1058G>C allele, which may be partial D and increase the risk of RHD alloantibody. The novel RHD1058G>C allele was inherited in three generations in a family rather than spontaneous mutation in an individual.