Identification of HLA-A*0111N: A Synonymous Substitution, Introducing an Alternative Splice Site in Exon 3, Silenced the Expression of an HLA-A Allele
Human Immunology, ISSN: 0198-8859, Vol: 66, Issue: 8, Page: 912-920
2005
- 27Citations
- 7Captures
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Metrics Details
- Citations27
- Citation Indexes26
- 26
- CrossRef22
- Patent Family Citations1
- Patent Families1
- Captures7
- Readers7
Article Description
A new variant of the HLA-A*010101 allele designated as HLA-A*0111N, previously known as HLA-A*010101var, was identified in a patient requiring a stem-cell transplantation. The patient was typed by serologic methods as HLA-A2 homozygous and by sequence-based typing (SBT) as A*010101,020601. Flow-cytometric (FCM) analysis with 11 human monoclonal antibodies (mAbs) for the A1 molecule confirmed lack of any cell membrane expression of the A*0111N allele. One-dimensional isoelectric focusing (1D-IEF) of total cell lysate from the patient’s cells revealed no cell surface and cytoplasmic A1 protein expression, whereas the HLA-A2 molecule was identified by both FCM analysis and 1D-IEF. DNA sequence analysis showed the presence of a synonymous substitution from G to T at position 597 in codon 175. RNA SBT revealed a deletion of 24 bp in exon 3, position 596 through 619, encoding codons 175 through 182 of the HLA-A*0111N allele. The synonymous substitution introduced a new splice site, resulting in an efficient splicing, because no classical A1 protein could be detected in the patient. This alternative splicing prevented the translation into a correct and stable class I molecule expression on the cell surface.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0198885905001199; http://dx.doi.org/10.1016/j.humimm.2005.06.010; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=26244440575&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/16216676; https://linkinghub.elsevier.com/retrieve/pii/S0198885905001199; https://dx.doi.org/10.1016/j.humimm.2005.06.010
Elsevier BV
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