title: Leukocyte adhesion deficiency: identification of novel mutations in two Japanese patients with a severe form.
abstract: Leukocyte adhesion deficiency is a disorder with mutations of the gene for the beta subunit, a component common to three adhesion molecules; LFA-1, Mac-1 and p150,95. The molecular basis of the disorder was studied in two patients with its severe form. In the first patient, the mutant gene expressed an aberrant mRNA, 1.2 kb longer than usual, resulting from a G to A substitution at the splice donor site of a 1.2 kb intron. Several aberrantly spliced messages, arising from splicing at cryptic donor sites, were also identified. The beta subunit proteins deduced from the mRNA sequences lacked half the carboxyl terminal portion. In the second patient, the mutation was a G to A transition at nucleotide 454, which resulted in an Asp128 to Asn substitution of the beta subunit. The 128th Asp residue is located in a region crucial for the association with alpha subunits and strictly conserved among the integrin beta subunits so far analyzed.
authors.affiliation: Department of Pediatrics, Yamaguchi University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Matsuura
authors.forename: F
authors.initials: F
authors.lastname: Kishi
authors.forename: M
authors.initials: M
authors.lastname: Tsukahara
authors.forename: H
authors.initials: H
authors.lastname: Nunoi
authors.forename: I
authors.initials: I
authors.lastname: Matsuda
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Kajii
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002478:Cells, Cultured; D002648:Child; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D005260:Female; D030342:Genetic Diseases, Inborn / Q000097:blood / Q000235:genetics*; D006801:Humans; D007438:Introns; D007564:Japan; D007962:Leukocytes / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics*; D046911:Macromolecular Substances; D016177:Macrophage-1 Antigen / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D012326:RNA Splicing; D012016:Reference Values; D012689:Sequence Homology, Nucleic Acid
chemical_list: D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D046911:Macromolecular Substances; D016177:Macrophage-1 Antigen; D009838:Oligodeoxyribonucleotides; D004247:DNA