Compound heterozygosity of two novel RHAG alleles leads to a considerable disruption of the Rh complex. Issue 4 (April 2016)

• Record Type: Journal Article
• Authors: Polin, Helene; Pelc‐Klopotowska, Monika; Danzer, Martin; Suessner, Susanne; Gabriel, Christian; Wilflingseder, Julia; Żmudzin, Alicja; Orzińska, Agnieszka; Guz, Katarzyna; Michalewska, Bogumila; Brojer, Ewa
• Is Part Of: Transfusion. Volume 56:Issue 4(2016:Apr.)
• Page Start: 950
• Page End: 955
• Publication Date: 2016-04
• Subjects: Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; Blood Group Antigens -- Periodicals; Blood Preservation -- Periodicals; Blood Transfusion -- Periodicals; 615
• DOI: 10.1111/trf.13476
• Languages: English
• ISSNs: 0041-1132

Abstract

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. STUDY DESIGN AND 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. CONCLUSION: 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.