Microcephaly-dystonia due to mutated PLEKHG2 with impaired actin polymerization
Microcephaly-dystonia due to mutated PLEKHG2 with impaired actin polymerization
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DOI：
10.1007/s10048-015-0464-y
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发表时间：
2016-01-01
期刊：
影响因子：
2.2
通讯作者：
Elpeleg, Orly
中科院分区：
文献类型：
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作者：
Edvardson, Simon;Wang, Haibo;Elpeleg, Orly
肌动蛋白骨架的重排是由rhogef激活的rhogtpase控制的。我们在5例重度精神发育迟滞、肌张力障碍、产后小头畸形和不同神经影像学模式的患者中发现了Rho胍交换因子（RhoGEF） PLEKHG2基因Arg204Trp突变的纯合性。突变体PLEKHG2的活性在基础状态和G - γ或溶血磷脂酸（LPA）刺激下均显著降低。sdf1a刺激的肌动蛋白聚合在患者细胞中显著受损，当PLEKHG2表达下调时，这种异常在对照细胞中重复。这些结果强调了PLEKHG2在肌动蛋白聚合中的作用，并描述了PLEKHG2缺乏的临床和放射学表现。
Rearrangement of the actin cytoskeleton is controlled by RhoGTPases which are activated by RhoGEFs. We identified homozygosity for Arg204Trp mutation in the Rho guanidine exchange factor (RhoGEF) PLEKHG2 gene in five patients with profound mental retardation, dystonia, postnatal microcephaly, and distinct neuroimaging pattern. The activity of the mutant PLEKHG2 was significantly decreased, both in basal state and when G beta gamma- or lysophosphatidic acid (LPA)-stimulated. SDF1a-stimulated actin polymerization was significantly impaired in patient cells, and this abnormality was duplicated in control cells when PLEKHG2 expression was downregulated. These results underscore the role of PLEKHG2 in actin polymerization and delineate the clinical and radiological findings in PLEKHG2 deficiency.