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Introduction The Lutheran (LU) blood group system consists of 19 antigens numbered 1���21 (LU10, LU15 designated obsolete). There are four pairs of allelic and polymorphic antigens; Lua/Lub(LU1/LU2), LU6/LU9, LU8/LU14 and Aua/Aub(LU18/LU19). The remaining 11 are all antigens of high frequency. For the majority of Lutheran antigens the molecular bases have been determined and their expression is nearly always associated with a single amino acid change in the Lu-glycoprotein. Lutheran antigens are carried on two red cell membrane glycoproteins, Lu-glycoprotein and epithelial cancer antigen. The two isoforms are encoded by a single gene LU located on chromosome 19q13.2 and organised into 15 exons. Case Study and Methods We investigated a case of a prenatal patient with no known history of transfusion or previous pregnancies, whose serum contained an antibody giving positive reactions with all donor cells tested. Serological tests were performed by standard agglutination techniques. Genomic DNA was isolated from whole blood of the patient, all the exons of the LU gene were amplified by PCR and directly sequenced. Results Serological tests confirmed the presence of a Lutheran antibody in the patient's serum. All tested cells were incompatible with the patient's serum, except several examples of Lu(a-b-) cells of both the dominant and recessive phenotype. Her red cells were tested with antibodies to high frequency Lutheran antigens and failed to react with anti-Lu4. Sequencing of the LU gene revealed a novel homozygous mutation in exon 5 524G>T, causing an amino acid change Arg175Leu in the protein. This novel mutation was found in the same codon (523CGG) in LU exon 5 as the only other known example of LU:-4, where the change at the same nucleotide was 524G>A, leading to Arg175Gln substitution. Conclusion We report the second individual with the rare LU:-4 phenotype. We have confirmed the patient's serum contained an anti-Lu4 antibody. This phenotype results from a single point mutation in LU leading to an Arg175Leu amino acid change in the protein. This new point mutation occurred at the same nucleotide as the mutation in the only other known example of LU:-4. However, it caused a different amino acid substitution than in the original example, indicating a potential hot spot for mutations in LU. |
