title: Description of 10 new mutations in platelet glycoprotein IIb (alphaIIb) and glycoprotein IIIa (beta3) genes.
abstract: In this study we have used denaturing gradient gel electrophoresis (DGGE) for identifying sequence alterations in glycoprotein (GP) IIb and IIIa genes from 20 patients affected by Glanzmann's thrombasthenia. These patients were from 16 different families. Using computer modelling, we divided the promoters, coding sequences and flanking splicing regions, in 31 segments for the GPIIb gene and 19 domains for the GPIIIa gene. We were able to find a mutation potentially affecting GPIIb-IIIa expression or function in 16 patients out of 20. In six patients from three families, the gypsy mutation modifying the splice donor site of intron 15 of the GPIIb gene was detected. In the other patients, 10 novel mutations were characterised, which were located either in the GPIIb gene (nine cases) or in the GPIIIa gene (one case). The type of mutation was nonsense mutation (one case), missense mutation (five cases), small insertion of 1 bp (one case) and splicing modifications (three cases). Among these genetic events, three were directly responsible for Glanzmann's thrombasthenia, four were localised in regions known to be involved in GPIIb-IIIa complex expression and three mutations were potentially responsible for Glanzmann's thrombasthenia.
authors.affiliation: Laboratoire d'Hémostase, Hospices Civils de Lyon, Hopital Edouard Herriot, INSERM U331, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Vinciguerra
authors.forename: J C
authors.initials: JC
authors.lastname: Bordet
authors.forename: G
authors.initials: G
authors.lastname: Beaune
authors.forename: C
authors.initials: C
authors.lastname: Grenier
authors.forename: M
authors.initials: M
authors.lastname: Dechavanne
authors.forename: C
authors.initials: C
authors.lastname: Négrier
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005091:Exons; D006801:Humans; D009154:Mutation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013915:Thrombasthenia / Q000235:genetics*
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex