Autosomal recessive spastic paraplegia 52 is caused by biallelic mutations in AP4S1 which encodes a subunit of the adaptor protein complex 4 (AP‐4). Using next‐generation sequencing, we identified three novel unrelated SPG52 patients from a cohort of patients with cerebral palsy. The discovered variants in AP4S1 lead to reduced AP‐4 complex formation in patient‐derived fibroblasts. To further understand the role of AP4S1 in neuronal development and homeostasis, we engineered the first zebrafish model of AP‐4 deficiency using morpholino‐mediated knockdown of ap4s1. In this model, we discovered several phenotypes mimicking SPG52, including altered CNS development, locomotor deficits, and abnormal neuronal excitability.

中文翻译：

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斑马鱼中 ap4s1 的缺失导致类似于痉挛性截瘫的神经发育缺陷 52。

常染色体隐性痉挛性截瘫 52 是由编码衔接蛋白复合物 4 (AP-4) 亚基的AP4S1中的双等位基因突变引起的。使用新一代测序，我们从一组脑瘫患者中确定了三名新的不相关的 SPG52 患者。发现的AP4S1变异导致患者来源的成纤维细胞中 AP-4 复合物的形成减少。为了进一步了解AP4S1在神经元发育和体内平衡中的作用，我们使用吗啉介导的ap4s1敲低设计了第一个 AP-4 缺陷斑马鱼模型。在这个模型中，我们发现了几种模仿 SPG52 的表型，包括改变的 CNS 发育、运动缺陷和异常的神经元兴奋性。