title: Glanzmann's thrombasthenia: identification of 19 new mutations in 30 patients.
abstract: Glanzmann's thrombasthenia (GT) is a genetically heterogeneous autosomal recessive syndrome associated with a bleeding tendency. To elucidate molecular basis of GT we have screened for mutations 30 GT patients. On the whole, 21 different candidate causal mutations, 17 in the alphaIIb and 4 in the beta3 gene have been found. Only two (alphaIIb Pro145Ala and IVS3(-3)-418del) have been previously reported. Nine mutations (42.9%) were likely to produce truncated proteins, whereas the remaining 12 were missense mutations that affected highly conserved residues in alphaIIb and beta3 genes. Six mutations were found in different patients suggesting a possible founder effect. The wide spectrum of expressivity, ranging from mild to severe also among patients carrying the same mutations, provided evidence for a role of different loci or circumstantial factors. In conclusion, we have identified a spectrum of unreported mutations that may be of value to unravel the role of specific regions of alphaIIb and beta3 genes.
authors.affiliation: Unità di Aterosclerosi e Trombosi, I.R.C.C.S. Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Andrea
authors.forename: Donatella
authors.initials: D
authors.lastname: Colaizzo
authors.forename: Gennaro
authors.initials: G
authors.lastname: Vecchione
authors.forename: Elvira
authors.initials: E
authors.lastname: Grandone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Minno
authors.forename: Maurizio
authors.initials: M
authors.lastname: Margaglione
mesh_terms: D000293:Adolescent; D000328:Adult; D020816:Amino Acid Motifs; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D007223:Infant; D039661:Integrin beta3 / Q000235:genetics; D007558:Italy; D008297:Male; D009154:Mutation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics; D040201:Platelet Membrane Glycoprotein IIb / Q000235:genetics; D016133:Polymerase Chain Reaction; D013915:Thrombasthenia / Q000235:genetics*
chemical_list: D017931:DNA Primers; D039661:Integrin beta3; D019038:Platelet Glycoprotein GPIb-IX Complex; D040201:Platelet Membrane Glycoprotein IIb