A family study of the Chinese Rhnull individual of the regulator type: a novel single missense mutation identified in RHAG gene.

Background: Rh(null) is a rare autosomal recessive disorder, and Rh(null) of the regulator type may result from mutation of the RHAG gene, which encodes RhAG glycoprotein and modulates Rh antigen expression. This study described the molecular genetic analysis of a Chinese Rh(null) family and identified a novel mutation in the RHAG gene.

Study Design And Methods: RBCs from the Rh(null) family members were analyzed for Rh phenotype by standard methods. DNA sequences of all 10 exons of RHAG gene were analyzed using genomic DNA by polymerase chain reaction and direct DNA sequencing.

Results: Genomic DNA analyses showed that a 672C>A mutation in Exon 5 of the RHAG gene was present at the homozygous state in DH and at the heterozygous state in the other members of the Rh(null) family. The 672C>A missense mutation converted serine into arginine at Position 224 in the Transmembrane Segment 7 of RhAG glycoprotein.

Conclusion: These findings provide evidence that the 672C>A missense mutation in the RHAG gene could result in Rh(null) of the regulator type, and the single-amino-acid change (Ser to Arg) might be critical for assembly of the Rh antigen complex within the membrane.