Platelets. 2013;24(1):77-80. doi: 10.3109/09537104.2012.665278. Epub 2012 Mar 6.
Mutation screening in Glanzmann thrombasthenia (GT) is now advanced. Despite the large number of genetic defects reported in the ITGA2B gene, few affect the structure of the N-terminal domain of the αIIb subunit. We now report a Catalan family where type I GT is given by compound heterozygosity within ITGA2B with a Gly13Val substitution in αIIb associated with a 13 bp deletion involving the splice site of exon 15. Molecular modelling confirmed that the Gly13Val mutation interfered with the structure of the αIIb β-propeller and confirms that a fold-back of the N-terminus to interact with residues deep within the propeller is necessary for the normal intracellular processing of the maturing αIIbβ3 integrin.
目前，对 Glanzmann 血小板无力症（GT）的突变筛查已经取得了进展。尽管在 ITGA2B 基因中已经报道了大量的遗传缺陷，但很少有缺陷会影响 αIIb 亚基的 N 端结构域的结构。我们现在报告了一个来自加泰罗尼亚的家族，其中 I 型 GT 是由 ITGA2B 内的复合杂合性引起的，与 αIIb 相关联的 Gly13Val 取代与涉及外显子 15 剪接位点的 13 bp 缺失有关。分子建模证实 Gly13Val 突变干扰了 αIIb β-螺桨的结构，并证实 N 端的折叠回与螺桨深处的残基相互作用对于成熟的 αIIbβ3 整合素的正常细胞内加工是必要的。
