Division of Newborn Medicine, Department of Medicine, Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Pediatr Neurol. 2011 Jul;45(1):49-53. doi: 10.1016/j.pediatrneurol.2011.02.004.
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.
双侧额顶叶脑回过多症是一种常染色体隐性遗传的人类脑畸形，具有异常的皮质分层。受影响的皮质似乎由许多小回组成，皮质-白质交界处呈扇贝状。伴有白质、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。GPR56 是致病基因。我们在此报道了一个新的 GPR56 错义突变 E496K，该突变在一个双侧额顶叶脑回过多症的近亲家系中被鉴定出来。GPR56 蛋白在 G 蛋白偶联受体蛋白酶切割位点被切割成 N-和 C-末端片段，分别命名为 GPR56(N)和 GPR56(C)。E496K 位于 GPR56(C)中。进一步的生化研究表明，该突变影响 GPR56(C)的细胞表面表达，类似于先前报道的突变 R565W 的影响。这些结果为 GPR56 突变如何导致神经疾病提供了进一步的见解。
