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High frequency of partial DIIIa and DAR alleles found in sickle cell disease patients suggests increased risk of alloimmunization to RhD
Author(s) -
Castilho L.,
Rios M.,
Rodrigues A.,
Pellegrino J.,
Saad S. T. O.,
Costa F. F.
Publication year - 2005
Publication title -
transfusion medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.471
H-Index - 59
eISSN - 1365-3148
pISSN - 0958-7578
DOI - 10.1111/j.1365-3148.2005.00548.x
Subject(s) - genotyping , allele , polymerase chain reaction , restriction fragment length polymorphism , loss of heterozygosity , compound heterozygosity , genotype , biology , genomic dna , allele frequency , antibody , genetics , microbiology and biotechnology , immunology , medicine , gastroenterology , gene
Summary. We have set out to determine the frequency of DIIIa and DAR alleles among sickle cell disease (SCD) patients. These D variants permit the unexpected development of antibodies to RhD among individuals who are otherwise classified as RhD + . DNA samples from 130 SCD patients were tested for 455A>C (specific for DIIIa), 602C>G, 667T>G (common for both DIIIa and DAR) and 1025T>C (specific for DAR) by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) and sequence analysis. The PCR‐RFLP showed that 12 (9·2%) of the SCD patients were carrying DIIIa and DAR alleles. Genomic DNA analysis performed by sequence showed that three samples were heterozygous DIIIa (2·3%), seven heterozygous DAR (4·6%) and two (1·5%) samples carried a partial D with four mutations: 455A>C (heterozygous), 602C>G and 667T>G (homozygous) and 1025T>C (heterozygous), indicating compound heterozygosity for one DIIIa allele and one DAR allele. The predicted phenotypes of eight (6·2%) SCD patients were DIIIa, DAR and DIIIa/DAR. Three patients were anti‐D immunized (DAR, n = 1; DIIIa/DAR, n = 2). These findings suggest that SCD patients who are candidates for chronic transfusion may benefit from genotyping for DIIIa and DAR to prevent alloimmunization.