Case of D-Variant from a Frameshift MutationRHD711delC

Abstract

D antigens are clinically significant, and routine tests on the D antigen requires the inclusion of weak D testing, which is performed using indirect antihuman immunoglobulin methods. On the other hand, exact typing of the D type of an individual can be done more precisely with RHD genotyping, which is a useful tool in cases where the RHD gene is intact. The majority of weak-D or partial-D cases are from single nucleotide changes or hybridization of RHD and RHCE genes. Nevertheless, frameshift mutations can also result in weak or partial-D. The characteristics of a frameshift mutation is typically a change in protein product after a problematic mutation and early termination of transcription, leading into truncated protein products. This paper reports a D-variant case with RHD 711delC along with a review of the relevant literature. In addition, the results of software analysis are reported. (Korean J Blood Transfus 2019;30:168-173)

Frameshift variations in the RHD coding sequence: Molecular mechanisms permitting protein expression

“…Among the 51 published frameshift variants in the RHD gene, the phenotype for 44 alleles has been reported (Table 1), 25–34 of which 36 alleles present a D‐negative phenotype, as expected. The remaining eight alleles express, however, some RhD protein; six were reported as DEL and two as weak D phenotype 6,35 …”

“…Among 11 alleles with "insertions," four alleles harbor de novo insertions and seven duplications. (Table 1), [25][26][27][28][29][30][31][32][33][34] of which 36 alleles present a D-negative phenotype, as expected. The remaining eight alleles express, however, some RhD protein; six were reported as DEL and two as weak D phenotype.…”

“… d RHD*93_94insT is also listed as RHD*93dupT ( RHD*01N.50 ) by ISBT; RHD*660delG is also listed as RHD*659delG ( RHD*01N.78 ) by ISBT; RHD*785delA listed as RhD‐negative in the original publication by Flegel et al, 30 DEL by Ma et al, 31 and both as DEL and RhD‐negative by ISBT; RHD*822delG incorrectly labelled as RHD*882delG in the original publication 32 and listed incorrectly as RhD‐negative by ISBT; RHD*993delC listed as DEL by ISBT may refer to the nucleotide deletion rather than the phenotype; RHD*1252_1253insT is also associated with AJ630375 in GenBank; RHD*702delG with RHD‐CE(2)‐D allele listed as MG496272 in GenBank; and RHD*745_759delinsAG is also listed as RHD*01N.30 by ISBT 25 . RHD*93delC listed as RHD*01N.31 by ISBT has been declared obsolete 6 …”