Molecular background of D(C)(e) haplotypes within the white population.

Autor: Noizat-Pirenne F; Blood Group National Reference Center, Paris, France. pirenne@ints.fr, Le Pennec PY, Mouro I, Rouzaud AM, Juszczak G, Roussel M, Lauroua P, Krause C, Rouger P, Cartron JP, Ansart-Pirenne H
Jazyk: angličtina
Zdroj: Transfusion [Transfusion] 2002 May; Vol. 42 (5), pp. 627-33.
DOI: 10.1046/j.1537-2995.2002.00097.x
Abstrakt: Background: D(C)(e) and D(C)e haplotypes may be encountered in the white population. Few data are available on the molecular backgrounds responsible for depressed expression of C and e.
Study Design and Methods: Individuals of white origin carrying a D(C)(e) genotype resulting in depressed expression of C or both C and e were subdivided into two categories based on the RBC reactivity with the human sera Mol and Hor, which contain antibodies against low-frequency antigens of the Rh (RH) system and other non-Rh low-frequency antigens. Neither Hor+, Mol+ nor Hor+, Mol- RBCs expressed the V (RH10), VS (RH20), and/or Rh32 (RH32) low-frequency antigens. These results suggested that Hor+, Mol+ variants expressed Rh33 (RH33 or Har) and FPTT (RH50), whereas Hor+, Mol- variants might express an undefined low-frequency antigen. Further serologic and molecular analyses were performed.
Results: Molecular analysis of Hor+, Mol+ variants revealed a hybrid gene structure RHCe-D(5)-Ce, in which exon 5 of RHCE (RHCe allele) was replaced by exon 5 of RHD (the so-called RHCeVA allele). The presence of exon 5RHD resulted in several amino acid alterations predicted in the external loop 4 of the CeVA polypeptide. Molecular analysis of Hor+, Mol- variants revealed the presence of a new RHCe allele characterized by a single point mutation C340T within exon 3 (the so-called RHCeMA allele), resulting in a R114W substitution predicted on the external loop 2 of the CeMA polypeptide. A serologic study showed a different pattern of reactivity with C and e MoAbs.
Conclusion: Two types of mutations resulted in amino acid substitutions predicted in external loops 4 and 2, respectively, which altered both the C and e reactivity, and indicated conformation changes or defective interaction between nonadjacent loops of the Ce polypeptide. Serologic analysis showed that together with Hor and Mol sera testing, the use of different C and e MoAbs could help to identify these variants within the white population.
Databáze: MEDLINE
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