D'Andrea Giovanna, Colaizzo Donatella, Vecchione Gennaro, Grandone Elvira, Di Minno Giovanni, Margaglione Maurizio
Unità di Aterosclerosi e Trombosi, I.R.C.C.S. Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Italy.
Thromb Haemost. 2002 Jun;87(6):1034-42.
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.
血小板无力症（GT）是一种具有遗传异质性的常染色体隐性综合征，与出血倾向相关。为阐明GT的分子基础，我们对30例GT患者进行了突变筛查。总体而言，已发现21种不同的候选致病突变，其中17种位于αIIb基因，4种位于β3基因。此前仅报道过两种（αIIb Pro145Ala和IVS3(-3)-418del）。9种突变（42.9%）可能产生截短蛋白，其余12种为错义突变，影响αIIb和β3基因中高度保守的残基。在不同患者中发现了6种突变，提示可能存在奠基者效应。同一突变患者中广泛的表达谱，从轻度到重度不等，为不同基因座或环境因素的作用提供了证据。总之，我们鉴定出一系列未报道的突变，这些突变可能有助于揭示αIIb和β3基因特定区域的作用。
