First report of Rh null individuals in the Indian population and characterization of the underlying molecular mechanisms

Rh phenotype is an extremely rare condition characterized by no expression of Rh antigens at the surface of red blood cells. Although rare, genetic bases of this phenotype are well known and include mutations within either the RH (RHD and RHCE) genes or the RHAG gene. So far Rh has been reported in...

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Bibliographic Details
Published in:Transfusion (Philadelphia, Pa.) Pa.), 2017-08, Vol.57 (8), p.1944-1948
Main Authors: Kulkarni, Swati S, Vasantha, Kasiviswanathan, Gogri, Harita, Parchure, Disha, Madkaikar, Manisha, Férec, Claude, Fichou, Yann
Format: Article
Language:English
Subjects:
Asian Continental Ancestry Group - genetics
Blood Proteins - genetics
Family
Female
Gene Deletion
Humans
India - epidemiology
Male
Membrane Glycoproteins - genetics
Pedigree
Rh-Hr Blood-Group System - genetics
RNA Splicing - genetics
Serologic Tests
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Summary:Rh phenotype is an extremely rare condition characterized by no expression of Rh antigens at the surface of red blood cells. Although rare, genetic bases of this phenotype are well known and include mutations within either the RH (RHD and RHCE) genes or the RHAG gene. So far Rh has been reported in individuals of Caucasian, African, and Asian origin. Here, we report individuals from two families of Indian origin representing such a rare phenotype. Serologic analysis was carried out by testing with anti-D, -C, -c, -E, and -e in Rh individuals and their family members. RH genes were analyzed by standard molecular approaches, including Sanger sequencing and quantitative multiplex polymerase chain reaction (PCR) of short fluorescent fragments. RHAG gene was investigated by exon-specific PCR amplification and Sanger sequencing. In one family, RHAG gene was found to be deleted at the homozygous state in the propositus, suggesting Rh of the regulator type. In the other family, a novel splice site variant in RHCE in cis with whole RHD gene deletion was identified at the homozygous state. Further functional analysis by minigene splicing assay showed that this variation, that is, c.801 + 1G>A, completely impairs normal splicing, then inactivating the expression of RhCE protein. Contrary to the former case, these data suggest Rh of the amorph type. Overall, we report for the first time the molecular mechanisms responsible for Rh phenotype in individuals of Indian origin. This study contributes to extend the molecular spectrum of variations in Rh individuals.
ISSN:0041-1132
1537-2995
DOI:10.1111/trf.14150