A Novel GPR56 Mutation Causes Bilateral Frontoparietal Polymicrogyria
A Novel GPR56 Mutation Causes Bilateral Frontoparietal Polymicrogyria
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DOI：
10.1016/j.pediatrneurol.2011.02.004
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发表时间：
2011-07-01
影响因子：
3.8
通讯作者：
Piao, Xianhua
中科院分区：
文献类型：
--
作者：
Luo, Rong;Yang, Hye Min;Piao, Xianhua
双侧额顶叶多小脑回症是一种常染色体隐性遗传的脑畸形，伴有皮质分层异常。受影响的皮质似乎由许多小回组成，皮质-白质交界处呈扇形。有相关的白色物质、脑干和小脑改变。受影响的个体表现为智力迟钝、语言障碍、运动发育迟缓和癫痫发作障碍。GPR 56为致病基因。在这里，我们报告了一个新的错义突变GPR 56，E496 K，确定在一个血缘家系与双边额顶叶polymicrogyria。GPR 56蛋白在G蛋白偶联受体蛋白水解位点被切割成N-和C-末端片段，分别称为GPR 56（N）和GPR 56（C）。E496 K位于GPR 56（C）中。进一步的生物化学研究表明，这种突变影响GPR 56（C）细胞表面表达，类似于先前报道的突变R565 W的效果。这些结果为GPR 56突变如何导致神经系统疾病提供了进一步的见解。(C)2011 Elsevier Inc. All rights reserved.
Bilateral frontoparietal polymicrogyria is an autosomal recessive inherited human brain malformation with abnormal cortical lamination. The affected cortex appears to consist of numerous small gyri, with scalloping of the cortical-white matter junction. There are associated white matter, brain stem, and cerebellar changes. Affected individuals manifest mental retardation, language impairment, motor developmental delay, and seizure disorder. GPR56 is the causative gene. Here we report a novel missense mutation of GPR56, E496K, identified in a consanguineous pedigree with bilateral frontoparietal polymicrogyria. GPR56 protein is cleaved at the G-protein-coupled receptor proteolytic site into an N- and a C-terminal fragment, named GPR56(N) and GPR56(C), respectively. E496K is located in GPR56(C). Further biochemical studies reveal that this mutation affects GPR56(C) cell surface expression similar to the effect of a previously reported mutation, R565W. These results provide further insights into how GPR56 mutation causes neurologic disease. (C) 2011 Elsevier Inc. All rights reserved.