A novel frameshift mutation in RHAG leads to Rh_null phenotype in a Chinese individual

We recently encountered a Rh_null phenotype proband within one family in the Chinese population. Rh_null is a rare autosomal recessive disorder characterized by the absence of the Rh antigens on the erythrocyte membrane, resulting in chronic hemolytic anemia. This study described the serological and molecular analysis of a Chinese Rh_null proband and his immediate family.

Red blood cells antigen phenotyping and antibody screening/identification were conducted. RHD, RHCE, and RHAG were analyzed using genomic DNA by polymerase chain reaction and sequence analysis.

Serologic tests showed a D-C-E-c-e- phenotype in the proband associated with the suspicion of anti-Rh29 (titer 16). Molecular analyses showed a new mutation (c.406dupA) in exon 3 of RHAG. This duplication introduced a reading frameshift (p.Thr136AsnfsTer21). The RHAG mutation was found in the homozygous state for the proband and heterozygous state for his parents.

We identified a novel RHAG mutation resulting in the Rh_null phenotype of the regulator type. Inheritance of the novel allele was shown by family study.