Early Infantile Epileptic Encephalopathy Associated With the Disrupted Gene Encoding Slit-Robo Rho GTPase Activating Protein 2 (SRGAP2)
Early Infantile Epileptic Encephalopathy Associated With the Disrupted Gene Encoding Slit-Robo Rho GTPase Activating Protein 2 (SRGAP2)
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DOI：
10.1002/ajmg.a.34363
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发表时间：
2012-01-01
影响因子：
2
通讯作者：
Matsumoto, Naomichi
中科院分区：
文献类型：
--
作者：
Saitsu, Hirotomo;Osaka, Hitoshi;Matsumoto, Naomichi
我们报告一位患有早期婴儿癫痫性脑病和严重精神障碍的女性患者，她有一个从头平衡易位t（1;9）（q32;q13）。患者出生后2天出现四肢阵挛性惊厥。脑电图（EEG）表现为一过性的非典型抑制-爆发模式。癫痫发作演变为短暂的强直性痉挛，在5个月大时注意到EEG上的心律失常，表明转变为West综合征。通过荧光原位杂交（FISH）、Southern杂交和反向PCR，成功地在核苷酸水平上确定了易位断裂点。1q32.1断裂点位于节段性重复内，并破坏了编码Slit-Robo Rho GT3激活蛋白2（SRGAP 2）的基因。9 q13断裂点位于异染色质区。Srgap 2在啮齿类动物发育中的脑中特异性表达，负调控神经元迁移，诱导神经突起生长和分支。因此，SRGAP 2很可能在人类大脑发育中发挥作用。这是第一次报告的SRGAP 2异常与早期婴儿癫痫性脑病。(C)2011 Wiley Periodicals，Inc.
We report on a female patient with early infantile epileptic encephalopathy and severe psychomotor disability possessing a de novo balanced translocation t(1;9)(q32;q13). The patient showed clonic convulsions of extremities 2 days after birth. Electroencephalogram (EEG) transiently showed atypical suppression-burst pattern. The seizures evolved to brief tonic spasms, and hypsarrhythmia on EEG was noticed at age of 5 months, indicating the transition to West syndrome. By using fluorescent in situ hybridization (FISH), southern hybridization, and inverse PCR, the translocation breakpoints were successfully determined at the nucleotide level. The 1q32.1 breakpoint was located within a segmental duplication and disrupted the gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2). The 9q13 breakpoint was suggested to reside in the heterochromatin region. Srgap2 has been shown to be specifically expressed in developing brain of rodents, negatively regulate neuronal migration and induce neurite outgrowth and branching. Thus, SRGAP2 is very likely to play a role in the developing human brain. This is a first report of the SRGAP2 abnormality associated with early infantile epileptic encephalopathy. (C) 2011 Wiley Periodicals, Inc.