Analysis of RHD genes in Taiwanese RhD‐negative donors by the multiplex PCR method

Abstract

The determination of the RhD phenotype is important in transfusion medicine. However, due to the complexity of D antigen expression, the routine serological method cannot differentiate all RhD variants. In addition, the induction of the anti-D antibody is still the major cause of severe hemolytic disease of the newborn (HDN). Therefore, it is important to understand RHD gene profiles. To analyze the RHD gene profiles of Taiwanese RhD-negative donors, the multiplex PCR method was applied to amplify RHD specific exons 3, 4, 5, 7, and 9. Based on the PCR results, the 156 RhD-negative donors were divided into 12 groups according to the different expression patterns of the RHD gene. These 12 groups were further divided into three categories: type I=Rh D(el) (21.8%); type II = partial D, containing some exons (9.0%); and type III = true RhD-negative (69.2%). The results indicated that 21.8% of RhD-negative donors in Taiwan were RhD(el), and 9% carried a part of the RHD gene. Six defined RhD variants were found in this study: four R(O) (Har), one D(Va), and two D(IVb). However, no true RhD-negative or RhD(el) donor with the CcdEe phenotype was found in this analysis.

Presence of RHD in serologically D–, C/E+ individuals: a European multicenter study

“…10,21,22 This regional specificity is further accentuated by the existence of an unexpressed RHD(G314V) allele contributing 13.8 percent to D negativity in Japanese (not including DELs), but its complete lack in the other two Asian populations investigated. [8][9][10][20][21][22] Taking into account the above-mentioned regional specificities, we aimed at investigating "the central European" allelism of D negativity among samples with positivity for either at least C or E. Participants were from Innsbruck (Austria), Oldenburg (Germany), Ljubljana (Slovenia), Bern (Switzerland), Braunschweig (Germany), and Kirov (Russia) and contributed between 54 and 738 samples, adding up to a total of 1700 samples investigated. Participating laboratories and their geographic locations are given in Fig.…”

“…In Asian persons-as shown by studies performed in Japan, Taiwan, and China-D negativity as detected by routine serologic methods includes a high percentage of DELs at a frequency in between 12.8 and 16.3 percent, whereas truly D-RHD-CE-D hybrid alleles are found at a comparably low frequency of in between 0.44 and 0.98 percent only. [8][9][10]20,21 It is noteworthy that apparently different region specific DEL alleles are responsible for their common high prevalence in Asian regions, even located close to each other, as exemplified by the Shenzen DEL lead allele RHD(K409K) and the Taiwan DEL lead allele RHD(delEx9) . 10,21,22 This regional specificity is further accentuated by the existence of an unexpressed RHD(G314V) allele contributing 13.8 percent to D negativity in Japanese (not including DELs), but its complete lack in the other two Asian populations investigated.…”

“…[8][9][10]20,21 It is noteworthy that apparently different region specific DEL alleles are responsible for their common high prevalence in Asian regions, even located close to each other, as exemplified by the Shenzen DEL lead allele RHD(K409K) and the Taiwan DEL lead allele RHD(delEx9) . 10,21,22 This regional specificity is further accentuated by the existence of an unexpressed RHD(G314V) allele contributing 13.8 percent to D negativity in Japanese (not including DELs), but its complete lack in the other two Asian populations investigated. [8][9][10][20][21][22] Taking into account the above-mentioned regional specificities, we aimed at investigating "the central European" allelism of D negativity among samples with positivity for either at least C or E. Participants were from Innsbruck (Austria), Oldenburg (Germany), Ljubljana (Slovenia), Bern (Switzerland), Braunschweig (Germany), and Kirov (Russia) and contributed between 54 and 738 samples, adding up to a total of 1700 samples investigated.…”

Molecular and family analyses revealed two novel RHD alleles in a survey of a Chinese RhD‐negative population

“…For instance, RhD‐negative in the Caucasians is primarily due to a deletion of whole RHD gene [1], while most RhD‐negative Africans have the RHD ‐pseudogene RHDΨ [2]. Among Asians, a certain percentage of RhD‐negative individuals have RHD‐CE‐D hybrid gene [3–8]. In the present work we investigated the molecular bases of 163 true RhD‐negative samples that do not express D antigen or lack functional RhD protein caused by the aberrant or absent RHD gene [9].…”

Molecular bases of unexpressed RHD alleles in Chinese D− persons

“…According to previous studies, the D− trait in Chinese individuals could arise from multiple genetic mechanisms 3‐8 . However, a comprehensive study of D− subjects is currently lacking.…”