Abstract：
The p21-activated kinase (PAK) family of proteins regulates various processes requiring dynamic cytoskeleton organization such as cell adhesion, migration, proliferation, and apoptosis. Among the six members of the protein family, PAK2 is specifically involved in apoptosis, angiogenesis, or the development of endothelial cells. We report a novel de novo heterozygous missense PAK2 variant, p.(Thr406Met), found in a newborn with clinical manifestations of Knobloch syndrome. In vitro experiments indicated that this and another reported variant, p.(Asp425Asn), result in substantially impaired protein kinase activity. Similar findings were described previously for the PAK2 p.(Glu435Lys) variant found in two siblings with proposed Knobloch syndrome type 2 (KNO2). These new variants support the association of PAK2 kinase deficiency with a second, autosomal dominant form of Knobloch syndrome: KNO2.
摘要：
p21激活的激酶（PAK）蛋白家族调节需要动态细胞骨架组织的各种过程，例如细胞粘附，迁移,扩散,和凋亡。在蛋白质家族的六个成员中，PAK2特异性参与细胞凋亡，血管生成,或内皮细胞的发育。我们报告了一种新的从头杂合错义PAK2变体，p.(Thr406Met)，在有Knobloch综合征临床表现的新生儿中发现。体外实验表明，这个和另一个报道的变体，p.（Asp425Asn），导致蛋白激酶活性显著受损。先前在两个兄弟姐妹中发现的PAK2p。（Glu435Lys）变体中发现了类似的发现，提出了2型Knobloch综合征（KNO2）。这些新的变体支持PAK2激酶缺乏与第二，常染色体显性遗传形式的Knobloch综合征：KNO2。
