title: Compound heterozygosity of two novel RHAG alleles leads to a considerable disruption of the Rh complex.
abstract: BACKGROUND
  The Rhesus (Rh) complex consists of a core comprising the Rh proteins (RhD/RhCE) and the Rh-associated glycoprotein (RhAG) with accessory chains (GPB, LW, CD47). Molecular defects of the RHAG gene may cause a regulator Rhnull phenotype without Rh antigen expression or a Rhmod phenotype with decreased Rh antigen expression.
  
  
  METHODS
  Blood samples of a donor with strongly diminished Rh antigens and five family members were analyzed by serological phenotyping, flow cytometry, molecular testing, and gene expression analysis of Rh complex candidate genes.
  
  
  RESULTS
  RHAG sequencing identified a missense mutation, c.241G>C (p.Gly81Arg) and a splice site mutation, c.640 + 3del14, among the cohort. Compound heterozygosity of these novel alleles identified in the propositus and two siblings gave rise to a strongly diminished expression of RhAG, Rh, and CD47 antigens on the RBC surface.
  
  
  CONCLUSIONS
  The Rhmod phenotype was caused by a novel RHAG splice site mutation in association with a non-functional allele. The primary depression of RhAG is most likely due to posttranslational events that affect the interaction and processing of the RhAG glycoprotein and gave rise to a secondary depression of RhD, RhCE, and CD47, the major members of the Rh complex.
authors.affiliation: Red Cross Transfusion Service of Upper Austria, Linz, Austria.|Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Linz, Austria.
authors.forename: Helene
authors.initials: H
authors.lastname: Polin
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Pelc-Klopotowska
authors.affiliation: Red Cross Transfusion Service of Upper Austria, Linz, Austria.|Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Linz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Danzer
authors.affiliation: Red Cross Transfusion Service of Upper Austria, Linz, Austria.|Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Linz, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Suessner
authors.affiliation: Red Cross Transfusion Service of Upper Austria, Linz, Austria.|Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Linz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Gabriel
authors.affiliation: Department of Nephrology, KH Elisabethinen, Linz, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Wilflingseder
authors.affiliation: Regional Blood Transfusion Center, Radom, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Żmudzin
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Orzińska
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Guz
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Bogumila
authors.initials: B
authors.lastname: Michalewska
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Brojer
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D012204:Rh-Hr Blood-Group System / Q000235:genetics* / Q000378:metabolism; D035781:Siblings
chemical_list: D001798:Blood Proteins; D008562:Membrane Glycoproteins; C498523:RHAG protein, human; D012204:Rh-Hr Blood-Group System