Mutations of schizophrenia risk gene SETD1A dysregulate synaptic function in human neurons.

ABSTRACT: Schizophrenia (SCZ) is a complex neuropsychiatric disorder associated with both common risk variants of small effect sizes and rare risk variants of high penetrance. Rare premature open reading frame (ORF) termination variants in SETD1A (SET Domain Containing 1A) show a strong association with SCZ; however, it remains largely unclear how rare premature ORF termination variants in SETD1A contribute to the pathophysiology of SCZ. To understand the impact of SETD1A rare premature ORF termination variants in human neurons, we CRISPR/Cas9-engineered five isogenic pairs of human induced pluripotent stem cells (iPSCs), with a recurrent heterozygous patient-specific premature ORF termination mutation c.4582-2delAG in two donor lines and a heterozygous frameshift mutation c.4596_4597insG (p. Leu153

SUBMITTER: Su X 

PROVIDER: S-EPMC12602330 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature