A novel HLA-b*39 allele (HLA-b*3916) due to a rare mutation causing cryptic splice site activation

Ryad Tamouza, Nahed El Kassar, Veronique Schaeffer, Etienne Carbonnelle, Zohreh Tatari Calderone, François Marzais, Catherine Fortier, Jean Claude Poirier, Khalid Sadki, Francoise Bernaudin, Antoine Toubert, Rajagopal Krishnamoorthy, Dominique Charron

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

A novel HLA-B*39 variant, found in an African patient with sickle cell anemia undergoing bone marrow transplantation is described. Initially suspected by inconsistent serological typing (B-blank, Bw6), then recognized by PCR-SSP, and finally characterized by nucleotide sequencing, this novel allele is designated HLA-B* 3916. It differs from HLA-B* 3910 by a point mutation (G to C) at position 17 of exon 3 causing glutamine to histidine change at codon 96 of α2 domain, a conserved position among HLA class I alleles, cDNA sequence analysis further revealed the presence of both normally and abnormally spliced mRNA species in established cell lines. The abnormal species correspond to partial truncation of exon 3 presumably due to the nucleotide change in exon 3, which constitutes a new consensus acceptor splice site within this exon. We postulate that the observed blank is essentially the consequence of qualitative change in a critical region of this novel antigen as abnormal mRNA species are relatively less abundant than normal species. Because the residue 96 of the HLA class I heavy chain is directly involved in interaction with α2m, another interesting possibility is that an aminoacid change in this position would perturb such interaction and consequently could affect the serological specificity of B* 3916, or its expression or both. (C) 2000 American Society for Histocompatibility and Immunogenetics.

Original languageEnglish
Pages (from-to)467-473
Number of pages7
JournalHuman Immunology
Volume61
Issue number5
DOIs
Publication statusPublished - May 2000
Externally publishedYes

Fingerprint

RNA Splice Sites
HLA-B Antigens
Exons
Alleles
Mutation
Nucleotides
Messenger RNA
Sickle Cell Anemia
Glutamine
Bone Marrow Transplantation
Point Mutation
Histidine
Codon
Sequence Analysis
Complementary DNA
Antigens
Cell Line
Polymerase Chain Reaction

Keywords

  • αm
  • B*39 variant
  • Cryptic splice site
  • HLA-B blank
  • Sickle cell disease

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

A novel HLA-b*39 allele (HLA-b*3916) due to a rare mutation causing cryptic splice site activation. / Tamouza, Ryad; El Kassar, Nahed; Schaeffer, Veronique; Carbonnelle, Etienne; Tatari Calderone, Zohreh; Marzais, François; Fortier, Catherine; Poirier, Jean Claude; Sadki, Khalid; Bernaudin, Francoise; Toubert, Antoine; Krishnamoorthy, Rajagopal; Charron, Dominique.

In: Human Immunology, Vol. 61, No. 5, 05.2000, p. 467-473.

Research output: Contribution to journalArticle

Tamouza, R, El Kassar, N, Schaeffer, V, Carbonnelle, E, Tatari Calderone, Z, Marzais, F, Fortier, C, Poirier, JC, Sadki, K, Bernaudin, F, Toubert, A, Krishnamoorthy, R & Charron, D 2000, 'A novel HLA-b*39 allele (HLA-b*3916) due to a rare mutation causing cryptic splice site activation', Human Immunology, vol. 61, no. 5, pp. 467-473. https://doi.org/10.1016/S0198-8859(00)00108-7
Tamouza, Ryad ; El Kassar, Nahed ; Schaeffer, Veronique ; Carbonnelle, Etienne ; Tatari Calderone, Zohreh ; Marzais, François ; Fortier, Catherine ; Poirier, Jean Claude ; Sadki, Khalid ; Bernaudin, Francoise ; Toubert, Antoine ; Krishnamoorthy, Rajagopal ; Charron, Dominique. / A novel HLA-b*39 allele (HLA-b*3916) due to a rare mutation causing cryptic splice site activation. In: Human Immunology. 2000 ; Vol. 61, No. 5. pp. 467-473.
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abstract = "A novel HLA-B*39 variant, found in an African patient with sickle cell anemia undergoing bone marrow transplantation is described. Initially suspected by inconsistent serological typing (B-blank, Bw6), then recognized by PCR-SSP, and finally characterized by nucleotide sequencing, this novel allele is designated HLA-B* 3916. It differs from HLA-B* 3910 by a point mutation (G to C) at position 17 of exon 3 causing glutamine to histidine change at codon 96 of α2 domain, a conserved position among HLA class I alleles, cDNA sequence analysis further revealed the presence of both normally and abnormally spliced mRNA species in established cell lines. The abnormal species correspond to partial truncation of exon 3 presumably due to the nucleotide change in exon 3, which constitutes a new consensus acceptor splice site within this exon. We postulate that the observed blank is essentially the consequence of qualitative change in a critical region of this novel antigen as abnormal mRNA species are relatively less abundant than normal species. Because the residue 96 of the HLA class I heavy chain is directly involved in interaction with α2m, another interesting possibility is that an aminoacid change in this position would perturb such interaction and consequently could affect the serological specificity of B* 3916, or its expression or both. (C) 2000 American Society for Histocompatibility and Immunogenetics.",
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