title: A novel HLA-B*39 allele (HLA-B*3916) due to a rare mutation causing cryptic splice site activation.
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 alpha(2) 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 alpha(2)m, 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.
authors.affiliation: Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint Louis and INSERM U396, Paris, France. tamouza@histo.chu-stlouis.fr
authors.forename: R
authors.initials: R
authors.lastname: Tamouza
authors.forename: N
authors.initials: N
authors.lastname: El Kassar
authors.forename: V
authors.initials: V
authors.lastname: Schaeffer
authors.forename: E
authors.initials: E
authors.lastname: Carbonnelle
authors.forename: Z
authors.initials: Z
authors.lastname: Tatari
authors.forename: F
authors.initials: F
authors.lastname: Marzais
authors.forename: C
authors.initials: C
authors.lastname: Fortier
authors.forename: J C
authors.initials: JC
authors.lastname: Poirier
authors.forename: K
authors.initials: K
authors.lastname: Sadki
authors.forename: F
authors.initials: F
authors.lastname: Bernaudin
authors.forename: A
authors.initials: A
authors.lastname: Toubert
authors.forename: R
authors.initials: R
authors.lastname: Krishnamoorthy
authors.forename: D
authors.initials: D
authors.lastname: Charron
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D005260:Female; D015235:HLA-B Antigens / Q000235:genetics*; D059946:HLA-B39 Antigen; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012326:RNA Splicing; D016364:Reading Frames; D012689:Sequence Homology, Nucleic Acid
chemical_list: D015235:HLA-B Antigens; D059946:HLA-B39 Antigen