Extensive clinical, serologic and molecular studies lead to the first reported Rh mod phenotype in Argentina

MUFARREGE, NICOLÁS; FRANCO, NOELIA; TRUCCO BOGGIONE, CAROLINA; ARNONI, CARINE; PAULAVENDRAME, TATIANE; BARTOLI, SONIA; ENSINCK, ALEJANDRA; PRINCIPI, CINTIA; LUJAN BRAJOVICH, MELINA; MATTALONI, STELLA; RIQUELME, BIBIANA; BIONDI, CLAUDIA; CASTILHO, LILIAN; COTORRUELO, CARLOS

TRANSFUSION

WILEY-BLACKWELL PUBLISHING, INC

Año: 2020

0041-1132

BACKGROUND: A highly reduced expression of Rhantigens in the erythrocyte membrane is the main featureof Rhmod, an extremely rare phenotype. Mutations withinRHAG gene, which encodes RhAG glycoprotein andmodulates Rh antigen expression and Rh complexformation, are the molecular events responsible for theRhmod phenotype. Here we report a clinical, serologic,and molecular study of an Argentinean proband with Rhdeficiency syndrome.MATERIALS AND METHODS: Rh antigens, RhAGand CD47 glycoproteins were studied by serologicmethods in the proband, her parents and sister. Osmoticfragility and viscoelastic parameters were also examined.RHD zygosity was analyzed by RFLP-PCR. RHD,RHCE, and RHAG genes were studied by Sangersequencing.RESULTS: No Rh antigens were detected in theproband by standard techniques. However, adsorptionelution and anti-RhAG tests showed that the propositawas Rhmod. Reduced expression of CD47, enhancedosmotic fragility, and surface viscosity alterations givingrise to spherocytes were observed in the patient.Sequencing analysis showed that a c.920C>T mutationin RHAG Exon 6 was present in a homozygous state inthe proband and in a heterozygous state in the rest ofthe family. This novel missense mutation caused the p.Ser307Phe amino acid substitution in TransmembraneSegment 10 of the RhAG glycoprotein.CONCLUSION: This comprehensive study determinedthe causes of the probandʼs anemia allowing thediagnosis of Rh-deficiency syndrome.