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

Abstract Background 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. Methods 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. Results 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. Conclusion 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.