Glanzmann’s Thrombasthenia: Identification of 19 New Mutations in 30 Patients

Summary

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 α_IIb and 4 in the β₃ gene have been found. Only two (α_IIb 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 α_IIb and β₃ 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 α_IIb and β₃ genes.

Keywords

Glanzmann’s Thrombasthenia - α_IIb and β₃ genes - mutations

^* The other contributors to this study are listed in the Appendix

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