title: A deletion in the second exon of an HLA-DRB1 allele found in a DR2-negative narcolepsy patient.
abstract: In this report, we describe a new allele of the HLA-DRB 1 gene carrying a form of mutation that has not been observed before. It appeared in an HLA-DR2-negative narcolepsy patient who, besides HLA-DR4, revealed a serologic HLA-DR blank segregating with HLA-DQ1. Oligotyping showed that the new allele belongs to the HLA-DR8 group. Restriction analysis and DNA sequencing revealed the deletion of 12 bp as well as the substitution of 9 flanking base pairs between codons 36 and 43. The expression of the mutated gene was demonstrated by the presence of its messenger RNA and a few positive reactions with DR8 sera. Without interrupting the reading frame, the mutation leads to a gene product composed of a modified amino acid sequence. We anticipate that the mutation influences the conformation of the molecule with possible consequences concerning immune response.
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Roushdy
authors.forename: S
authors.initials: S
authors.lastname: Santoso
authors.forename: R
authors.initials: R
authors.lastname: Kalb
authors.forename: K
authors.initials: K
authors.lastname: Meier-Ewert
authors.forename: E D
authors.initials: ED
authors.lastname: Albert
authors.forename: G
authors.initials: G
authors.lastname: Mueller-Eckhardt
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D005091:Exons; D005260:Female; D017353:Gene Deletion; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009290:Narcolepsy / Q000235:genetics* / Q000276:immunology; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger