title: Short duplication within the RHCE gene associated with an in cis deleted RHD causing a Rhnull amorph phenotype in an immunized pregnant woman with anti-Rh29.
abstract: BACKGROUND
  The rare amorph Rhnull phenotype is caused by silent alleles at the RH locus and usually arises in consanguineous families. To date, only five molecular backgrounds have been identified in five unrelated families. Subjects with Rhnull red blood cells (RBCs) readily produce alloantibodies to high-prevalence Rh antigens.
  
  
  METHODS
  RBCs from a pregnant woman (G5P3) from Libya, with a positive indirect antiglobulin test were phenotyped by hemagglutination. RHD and RHCE genes were analyzed at the genomic level and mutation inheritance pattern was assessed in the patient's family.
  
  
  RESULTS
  Hemagglutination testing showed a D-C-E-c-e- phenotype in the proposita associated with the presence of a high titer anti-Rh29 (4096). Molecular analysis revealed a deletion of RHD and presence of a novel RHCE allele with a 7-bp duplication in Exon 7. This duplication is predicted to introduce a frameshift after His350, a new C-terminal sequence, and a premature stop codon resulting in shortened predicted protein with only 402 amino acids. The mutated allele was found at homozygous state in the proposita and heterozygous state in her parents and one brother.
  
  
  CONCLUSIONS
  This report describes a novel RHCE mutation causing the loss of RhCE antigen expression in association with RHD deletion, leading to an amorph Rhnull phenotype.
authors.affiliation: Etablissement Français du Sang Alpes Méditerranée, Marseille, France.|UMR 7268 ADÉS Aix-Marseille Université-EFS-CNRS, Marseille, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Silvy
authors.affiliation: Etablissement Français du Sang Alpes Méditerranée, Marseille, France.|UMR 7268 ADÉS Aix-Marseille Université-EFS-CNRS, Marseille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Beley
authors.affiliation: Département Centre National de Référence pour les Groupes Sanguins, Institut National de la Transfusion Sanguine (INTS), Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Peyrard
authors.affiliation: Centre Régional de Transfusion Sanguine, Unité de Recherche UR12SP26, Sousse, Tunisia.
authors.forename: Mouna
authors.initials: M
authors.lastname: Ouchari
authors.affiliation: Centre Régional de Transfusion Sanguine, Unité de Recherche UR12SP26, Sousse, Tunisia.
authors.forename: Saadia
authors.initials: S
authors.lastname: Abdelkefi
authors.affiliation: Centre Régional de Transfusion Sanguine, Unité de Recherche UR12SP26, Sousse, Tunisia.
authors.forename: Saloua
authors.initials: S
authors.lastname: Jemni Yacoub
authors.affiliation: Etablissement Français du Sang Alpes Méditerranée, Marseille, France.|UMR 7268 ADÉS Aix-Marseille Université-EFS-CNRS, Marseille, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Chiaroni
authors.affiliation: Etablissement Français du Sang Alpes Méditerranée, Marseille, France.|UMR 7268 ADÉS Aix-Marseille Université-EFS-CNRS, Marseille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Bailly
mesh_terms: D000328:Adult; D000745:Anemia, Hemolytic, Congenital / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D020440:Gene Duplication; D006801:Humans; D007114:Immunization; D008002:Libya; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D012203:Rh Isoimmunization / Q000276:immunology / Q000517:prevention & control; D012204:Rh-Hr Blood-Group System / Q000235:genetics*; D018029:Rho(D) Immune Globulin / Q000276:immunology / Q000627:therapeutic use*
chemical_list: C066468:RHCE protein, human; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin; C026410:Rho(D) antigen