精神发育迟缓（MR）是最常见的儿童大脑发育障碍性疾病之一，我国儿童患病率达0.93%，且50%以上MR患儿病因不明，急需对其致病原因及发病机制进行深入研究，以为临床治疗提供线索。我们通过全基因组拷贝数变异分析和全外显子测序发现3例MR患儿存在Slp3基因缺失或突变。Slp3蛋白主要参与不同组织细胞内囊泡转运和细胞极性的建立，但其在神经系统中的作用尚无相关报导。我们前期研究结果发现，Slp3敲除的人胚胎干细胞来源皮层神经细胞的迁移显著增加，成熟皮层神经元兴奋性突触后电流的频率明显降低。同时，胚胎电转敲低小鼠VZ区神经干细胞中Slp3的表达显著增加小鼠皮层神经细胞的迁移。这些结果提示：Slp3在人和小鼠皮层神经发育中具有重要作用。本研究将在前期结果的基础上，进一步研究Slp3及其相互作用蛋白调控皮层发育的作用及机制，并结合病人诱导性多能干细胞解析Slp3基因变异导致脑发育迟缓的作用机理。

Mental Retardation (MR) is the most common brain developmental disease. In China, the prevalence of MR is 0.93% in children which 50% with unknown reason. Thus, it is urgent to study the underlying pathogenesis to provide clues for clinical treatment. Our previous data found 3 patients with MR by whole genome CNV analysis and full exon sequencing had Synaptotagmin like protein 3 (Slp3) gene deletion or missense mutation. Slp3 is mainly involved in transportation of intracellular vesicles and establishment of cell polarity in different types of cells from the body. However, the role of Slp3 in the nervous system has not been reported till now. Our previous experiments showed that Slp3 knockout significantly increased the migration of human embryonic stem cells derived cortical neuronal cells and dramatically decreased the excitatory postsynaptic currents in the mature cortical neuron. Similarly, knock down Slp3 gene expression in stem cell of ventral zone by IUE (in utero electroporation) revealed that cortical neuron migration significantly increased in developmental mice brain. These data suggest that Slp3 play an important roles during human and mice brain development, but the underlying mechanism is not clear. In the present study, we will further study the functions of Slp3 and its interacting proteins in regulation of cortical development, and explore the pathogenesis of mental retardation caused by Slp3 gene mutation by induced pluripotent stem cells from patients.