Table_1_Case report: A novel frameshift mutation in BRSK2 causes autism in a 16-year old Chinese boy.XLSX

Serine/threonine protein kinases are involved in axon formation and neuronal polarization and have recently been implicated in autism spectrum disorder (ASD) and neurodevelopmental disorders (NDD). Here, we focus on BRSK2, which encodes brain-specific serine/threonine protein kinase 2. Although previous studies have reported 19 unrelated patients with BRSK2 pathogenic variation, only 15 of 19 patients have detailed clinical data. Therefore, more case reports are needed to enrich the phenotype associated with BRSK2 mutations. In this study, we report a novel de novo frameshift variant (c.442del, p.L148Cfs*39) identified by exome sequencing in a 16 year-old Chinese boy with ASD. The proband presented with attention-deficit, auditory hallucinations, limb tremor, and abnormal brain electrical activity mapping. This study expands the phenotypic spectrum of BRSK2-related cases and reveals the highly variable severity of disorders associated with BRSK2.

丝氨酸/苏氨酸蛋白激酶参与轴突形成和神经元极化，近期研究表明其与自闭症谱系障碍（ASD）和神经发育障碍（NDD）有关。本研究聚焦于编码脑特异性丝氨酸/苏氨酸蛋白激酶2的BRSK2基因。尽管先前研究报道了19例与BRSK2致病性变异相关的患者，但其中仅有15例提供了详细的临床数据。因此，需要更多的病例报告来丰富与BRSK2突变相关的表型。在本研究中，我们报道了一名16岁中国男孩通过外显子测序鉴定出的一个新型无义突变（c.442del，p.L148Cfs*39），该突变与ASD相关。患者表现出注意力缺陷、听觉幻觉、肢体震颤和异常的脑电图。本研究扩展了BRSK2相关病例的表型谱系，并揭示了与BRSK2相关的疾病严重程度的高度可变性。