PDF(Sci-hub)
Abstract：
The primary anatomical defect leading to periventricular nodular heterotopia occurs within the neural progenitors along the neuroepithelial lining of the lateral ventricles and results from a defect in the initiation of neuronal migration, following disruption of the neuroependyma and impaired neuronal motility. Growing evidence indicates that the FLNA-dependent actin dynamics and regulation of vesicle formation and trafficking by activation of ADP-ribosylation factors (ARFs) can play an important role in this cortical malformation. We report the first inherited variant of ARF1 in a girl with intellectual disability and periventricular nodular heterotopia who inherited the variant from the father with previously undiagnosed single nodular heterotopia and mild clinical expression. Additionally, both patients presented some features suggestive of hypohidrotic ectodermal dysplasia. These clinical features showed similarities to those of three previously reported cases with ARF1 missense variants, confirming that haploinsufficiency of this gene causes a recognisable neurological disorder with abnormal neuronal migration and variable clinical expressivity.
摘要：
导致脑室周围结节性异位症的主要解剖缺陷发生在沿侧脑室神经上皮衬里的神经祖细胞内，并且是由于神经元迁移开始的缺陷所致。在神经室管膜破坏和神经元运动性受损后。越来越多的证据表明，依赖FLNA的肌动蛋白动力学以及通过激活ADP-核糖基化因子（ARF）对囊泡形成和运输的调节可能在这种皮质畸形中起重要作用。我们报告了一个患有智力障碍和脑室周围结节性异位症的女孩中ARF1的第一个遗传变体，该女孩从父亲那里继承了该变体，先前未诊断为单个结节性异位症，临床表现温和。此外,两名患者均表现出一些提示汗性外胚层发育不良的特征。这些临床特征与先前报道的三例ARF1错义变异病例相似，证实该基因的单倍体不足会导致可识别的神经系统疾病，具有异常的神经元迁移和可变的临床表达。
