Rare heterozygous deletions in the neurexin 1 (NRXN1) gene robustly increase an individual's risk of developing neurological and psychiatric disorders. However, the molecular bases by which different mutations result in different clinical presentations, with variable penetrance, are unknown. To better understand the molecular and cellular consequences of heterozygous NRXN1 mutations, Flaherty and colleagues studied how patient mutations influence the NRXN1 isoform repertoire and neuronal phenotypes using induced pluripotent stem (iPS) cells. Advancing from disease association to mechanistic insights, the authors provide insight into how patient mutations might impinge on neuronal function. This research highlights the value of iPS cells for elucidating otherwise elusive links between molecular and neuronal function. In addition, they provide further evidence of the importance of alternative splicing in the pathophysiology of neuropsychiatric diseases.

中文翻译：

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使用人类诱导的多能干细胞揭示神经精神疾病中患者特异性 NRXN1 突变的机制。

neurexin 1 (NRXN1) 基因中罕见的杂合缺失大大增加了个体患神经和精神疾病的风险。然而，不同的突变导致不同的临床表现和不同的外显率的分子基础是未知的。为了更好地了解杂合 NRXN1 突变的分子和细胞后果，Flaherty 及其同事使用诱导多能干 (iPS) 细胞研究了患者突变如何影响 NRXN1 同种型库和神经元表型。从疾病关联到机制见解，作者提供了有关患者突变如何影响神经元功能的见解。这项研究强调了 iPS 细胞在阐明分子和神经元功能之间难以捉摸的联系方面的价值。此外，