Description of 10 new mutations in platelet glycoprotein IIb (alpha IIb) and glycoprotein IIIa (beta 3) genes

In this study we have used denaturing gradient gel electrophoresis (DGGE) f or identifying sequence alterations in glycoprotein (GP) IIb and IIIa genes from 20 patients affected by Glanzmann's thrombasthenia. These patients we re from 16 different families. Using computer modelling, we divided the pro moters, 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 m utation potentially affecting GPIIb-IIIa expression or function in 16 patie nts out of 20. In six patients from three families, the gypsy mutation modi fying the splice donor site of intron 15 of the GPIIb gene was detected. In the other patients, 10 novel mutations were characterised, which were loca ted 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 potentia lly responsible for Glanzmann's thrombasthenia.