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.
Journal article
2020-09-01T00:00:00+00:00
29
1142 - 1144
2
NRXN1, disease modeling, human induced pluripotent stem cells, neuron, neuropsychiatric diseases, splicing, Calcium-Binding Proteins, Heterozygote, Humans, Induced Pluripotent Stem Cells, Mental Disorders, Mutation, Neural Cell Adhesion Molecules, Neurons