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PLASTIC RECONSTRUCTIVE AND REGENERATIVE SURGERY

Abstract

Background -  Among 195 known RHCE alleles, 10 have evolved to form hybrid RHCE-D-CE alleles encoding aberrant RhCE proteins lacking CE antigen expression. The resulting D-- phenotype predisposes to anti-Hro alloimmunization (anti-Rh17). Although hybrid alleles may appear identical at the mRNA level, distinct breakpoint configurations can result in diverse D phenotypes or Rh antigens. We determined the molecular structure of a D-- phenotype. An unrelated RHD allele, DMA  had been observed once without serology. We tested Rh antigen densities.

Materials and methods - Genomic DNA and cDNA were analyzed using a combination of molecular techniques and commercial red cell genotyping assays targeting the RHD and RHCE genes. A flow cytometric method was developed to quantify RhAG antigen expression. Red cell antigen densities were determined for RhAG and RhD in the D-- and DMA/DAU3 samples serologically.

Results - Nucleotide sequencing of the RHCE gene and its cDNA identified a homozygous CE-D(2–9)-CE hybrid allele in an individual of Afghan origin. The 5′ and 3′ breakpoint regions included 131 and 4,287 nucleotides. The new allele was linked in a haplotype to the normal RHD allele (RHD*01). Quantitative flow cytometry demonstrated antigen densities of 92,297 RhD and 52,907 RhAG molecules per red cell for the D-- sample (12,465 RhD and 117,871 RhAG for DMA/DAU3).

Discussion - We describe the breakpoint regions of a Ce–D(2–9)–Ce allele that encoded a D-- phenotype. Our results underscore the importance of breakpoint characterization for identifying clinically relevant RH variants and advancing personalized transfusion medicine. The second DMA observation, in trans to a DAU3 allele, aligned with a weak D phenotype for DMA.

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Authors

Kshitij Srivastava Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, United States of America ORCID

Caroline Ballard Dixon Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda

Marina Ursula Bueno Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, United States of America ORCID

Katharina Schallmoser Department for Transfusion Medicine, Paracelsus Medical University of Salzburg, Salzburg, Austria ORCID

Lydia Gruener Department for Transfusion Medicine, Paracelsus Medical University of Salzburg, Salzburg, Austria ORCID

Willy Albert Flegel Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, United States of America ORCID

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