TY - JOUR
T1 - Molecular background of VS and weak C expression in blacks
AU - Faas, B. H.
AU - Beckers, E. A.
AU - Wildoer, P.
AU - Ligthart, P. C.
AU - Overbeeke, M. A.
AU - Zondervan, H. A.
AU - von dem Borne, A. E.
AU - van der Schoot, C. E.
PY - 1997
Y1 - 1997
N2 - The Rh system is complex and consists of as many as 45 different antigens. Red cells of about 25 percent of the black population carry VS an Rh-system antigen (Rh20), but this antigen is very rare in whites. VS positivity is always associated with a weak expression of e, and usually also of C. The RH genes of 11 black VS-positive donors were studied. Transcripts were sequenced for four VS-positive donors, three of whom had red cells with a weak expression of C. In the other donors, only analysis of genomic DNA was carried out. The occurrence of VS was shown to be related to a single-point mutation in exon 5 of the RHCE gene (cytosine 733 guanine, leading to the Leu245Val substitution). The presence of this polymorphism in exon 5 may explain the simultaneously occurring weak e, because the E/e polymorphism is located in the same exon. Study of VS-positive donors with different Rh phenotypes showed that the polymorphism can occur in different alleles of the RHCE gene. In all three donors whose red cells showed a weak expression of C, a hybrid D-CE-D transcript was found, containing exon 4, 5, 6, 7, and (probably) 8 from the RHCE gene. No transcripts were encountered carrying DNA markers normally associated with C expression. It is therefore postulated that the hybrid gene is responsible for the weak expression of C in these individuals. The hybrid gene carried a Leu62Phe substitution, as well as the Leu245Val substitution responsible for VS. The gene most probably cosegregates with a C allele encoding Cys 16 (normally encoded only by the C allele) and Val245 (responsible for VS antigenicity when encoded by the RHCE gene). This explains the combination of weak expression of C and VS positivity that is frequently found in blacks
AB - The Rh system is complex and consists of as many as 45 different antigens. Red cells of about 25 percent of the black population carry VS an Rh-system antigen (Rh20), but this antigen is very rare in whites. VS positivity is always associated with a weak expression of e, and usually also of C. The RH genes of 11 black VS-positive donors were studied. Transcripts were sequenced for four VS-positive donors, three of whom had red cells with a weak expression of C. In the other donors, only analysis of genomic DNA was carried out. The occurrence of VS was shown to be related to a single-point mutation in exon 5 of the RHCE gene (cytosine 733 guanine, leading to the Leu245Val substitution). The presence of this polymorphism in exon 5 may explain the simultaneously occurring weak e, because the E/e polymorphism is located in the same exon. Study of VS-positive donors with different Rh phenotypes showed that the polymorphism can occur in different alleles of the RHCE gene. In all three donors whose red cells showed a weak expression of C, a hybrid D-CE-D transcript was found, containing exon 4, 5, 6, 7, and (probably) 8 from the RHCE gene. No transcripts were encountered carrying DNA markers normally associated with C expression. It is therefore postulated that the hybrid gene is responsible for the weak expression of C in these individuals. The hybrid gene carried a Leu62Phe substitution, as well as the Leu245Val substitution responsible for VS. The gene most probably cosegregates with a C allele encoding Cys 16 (normally encoded only by the C allele) and Val245 (responsible for VS antigenicity when encoded by the RHCE gene). This explains the combination of weak expression of C and VS positivity that is frequently found in blacks
U2 - https://doi.org/10.1046/j.1537-2995.1997.37197176949.x
DO - https://doi.org/10.1046/j.1537-2995.1997.37197176949.x
M3 - Article
C2 - 9024488
SN - 0041-1132
VL - 37
SP - 38
EP - 44
JO - Transfusion
JF - Transfusion
IS - 1
ER -