Molecular genetic analysis of the Japanese amorph Rhnull phenotype

Department of Legal Medicine and Human Genetics, Jichi-Medical School, Tochigi Japan
Transfusion (Impact Factor: 3.53). 04/2002; 40(5):617 - 618. DOI: 10.1046/j.1537-2995.2000.40050617.x
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    ABSTRACT: The deficiency of Rh proteins on red blood cells (RBCs) from individuals of the Rh(null) amorph type are the result of homozygosity for a silent RHCE in cis with a deleted RHD. A novel mutation in RHce was identified in two Caucasian Brazilian girls with the amorph type of Rh(null) who were born to parents who were first cousins. RBCs from the Rh(null) sisters and from family members were analyzed by serology and flow cytometry with specific antibodies. Genomic DNA and transcripts were tested by polymerase chain reaction and sequence analysis. Rh(null) RBCs were nonreactive with anti-Rh and anti-LW. Molecular analyses showed a deletion of RHD and of one nucleotide (960/963; GGGG-->GGG) in exon 7 of the RHce. This deletion introduced a frameshift after Gly321, a new C-terminal sequence, and a premature stop codon, resulting in a shorter predicted protein with 357 amino acids. The detection of a unique RHce transcript indicated that the two sisters were homozygous, whereas the other family members were heterozygous for the mutation. A novel mutation resulting in the amorph Rh(null) with loss of Rh antigen expression is described.
    Transfusion 11/2005; 45(11):1796-8. · 3.53 Impact Factor
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    ABSTRACT: The Rh system clinically is one of the important blood groups. The major Rh antigens, which are constituted by over 40 types, are RhD, RhC/c, and RhE/e. Furthermore, Rh blood group system is characterized by the existence of many variants. It was considered that Rh blood group system was encoded on two genes termed the RHCE and RHD, which are composed of ten exons, respectively. It is inferred that the RHD gene encodes the RhD antigen and that the RHCE gene encodes the Rh C/c and RhE/e antigens. There are RHce, RHCe, RHcE and RHCE alleles as polymorphisms of RHCE gene. In 2000, the entire nucleotide sequences in all introns of both the RHD and RHCE genes were determined. Due to the new findings on RH genes, it is thought that multiple recombination (and/or gene conversion), nucleotide substitutions, small nucleotide gaps, replication slippage of microsatellite, large nucleotide gaps (due to Alu sequence) and the high level of the homology (%) between both RH genes are the important factors in the formation and evolution of both RH genes and Rh variants. Based on the advance of human genome project, the new interpretations on the evolution and formation of RH genes and Rh variants will be performed. Human Rh family (superfamily) and its counterparts in primates, mammals, fish, amphibians, bacteria, lower eukaryotes, archaea and plants have been identified. A lot of findings have been accumulated in their evolution and function. As gene conversions or recombination events confuse the phylogenetic tree of human RH genes and their counterparts, careful attention is necessary for researchers to calculate the time of gene duplication and to discuss the evolution of Rh family and its counterparts.Rh genotyping methods will never be perfect and both the clinicians and researchers have to recognize the limitation of Rh genotyping, especially RhD genotyping, because new Rh variants must have formed continually. In applying the Rh genotyping to clinical medicine, especially transfusion medicine, it is necessary to compare and examine the serological (phenotypic) data in Rh blood group system with caution.
    Legal Medicine 10/2002; 4(3):139-55. · 1.08 Impact Factor
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    ABSTRACT: Blood group antigens (BGAs) can act as functional molecules but also can evoke autoantibodies and alloantibodies, causing autoimmune hemolytic anemia, hemolytic disease of the newborn and hemolytic transfusion reactions. In Section I, Dr. Marilyn Telen discusses physiologic and pathologic functions of RBC BGA-bearing molecules. She reviews some associations of BGAs with RBC membrane integrity and hemolytic anemia; association of BGAs with enzymatic and transport functions; and adhesion molecules expressed by RBCs, especially with reference to their pathophysiological role in sickle cell disease. In Section II, Dr. Lawrence Petz discusses the problems of providing blood for patients who have RBC autoantibodies. He provides an algorithm for excluding the presence of "hidden" alloantibodies, when all units appear to be incompatible due to the autoantibody. He emphasizes that clinicians should be aware of these approaches and not accept "the least incompatible unit." In Section III, Dr. George Garratty describes two processes, in development, that produce RBCs that result in RBCs that can be described as "universal" donor or "stealth" RBCs. The first process involves changing group A, B, or AB RBCs into group O RBCs by removing the immunospecific sugars responsible for A and B specificity by using specific enzymes. The second process involves covering all BGAs on the RBC surface using polyethylene glycol (PEG). Results of in vitro and in vivo studies on these modified RBCs are discussed.
    Hematology 02/2002; · 1.49 Impact Factor