ArticleAmerican journal of human genetics2022
Loss of function of OTUD7A in the schizophrenia- associated 15q13.3 deletion impairs synapse development and function in human neurons.
Article in American journal of human genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Targeting OTUD7A-HINT1 deubiquitination activates mTOR signaling for CNS regeneration.Cell death & disease · 2026Article
- Genetic Variants from Large Cohorts and Familial Studies Implicate Common Mechanisms in Schizophrenia.Biology · 2026Review
- How copy number variations shape brain developmental disorders: Unraveling the synaptic puzzle.Psychiatry and clinical neurosciences · 2026Review
- The effect of human-specific genetic variants on neuronal spinogenesis.Frontiers in genetics · 2026Review
- Prenatal diagnosis of 15q13.3 deletion and duplication syndrome: what do we tell the prospective parents?Archives of gynecology and obstetrics · 2025Article
- Mutations of schizophrenia risk gene SETD1A dysregulate synaptic function in human neurons.Molecular psychiatry · 2025Article
- Psychiatric Genomics 2025: State of the Art and the Path Forward.The Psychiatric clinics of North America · 2025Review
- Activation and Reactivity of the Deubiquitinylase OTU Cezanne-2 from MD Simulations and QM/MM Calculations.Journal of chemical information and modeling · 2025Article
- Region-Based Analyses of Existing Genome-Wide Association Studies Identifies Novel Potential Genetic Susceptibility Regions for Glioma.Cancer research communications · 2024Article
- Harnessing stem cell-based approaches for clinically meaningful discoveries in schizophrenia.Schizophrenia research · 2024Article
- Modeling common and rare genetic risk factors of neuropsychiatric disorders in human induced pluripotent stem cells.Schizophrenia research · 2024Review
- Progress towards understanding risk factor mechanisms in the development of autism spectrum disorders.Biochemical Society transactions · 2024Review
- Mechanisms of copy number variants in neuropsychiatric disorders: From genes to therapeutics.Current opinion in neurobiology · 2023Review
- The OTUD7A-Ankyrin pathway: a newly identified disease mechanism for the 15q13.3 microdeletion disorder.Molecular psychiatry · 2023Article
- Neurodevelopmental disturbances in schizophrenia: evidence from genetic and environmental factors.Journal of neural transmission (Vienna, Austria : 1996) · 2023Review
- Brain Lipids and Lipid Droplet Dysregulation in Alzheimer's Disease and Neuropsychiatric Disorders.Complex psychiatryReview
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Authors and funding
17 authors at 5 institutions in 1 country.
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Abstract
Identifying causative gene(s) within disease-associated large genomic regions of copy-number variants (CNVs) is challenging. Here, by targeted sequencing of genes within schizophrenia (SZ)-associated CNVs in 1,779 SZ cases and 1,418 controls, we identified three rare putative loss-of-function (LoF) mutations in OTU deubiquitinase 7A (OTUD7A) within the 15q13.3 deletion in cases but none in controls. To tie OTUD7A LoF with any SZ-relevant cellular phenotypes, we modeled the OTUD7A LoF mutation, rs757148409, in human induced pluripotent stem cell (hiPSC)-derived induced excitatory neurons (iNs) by CRISPR-Cas9 engineering. The mutant iNs showed a ∼50% decrease in OTUD7A expression without undergoing nonsense-mediated mRNA decay. The mutant iNs also exhibited marked reduction of dendritic complexity, density of synaptic proteins GluA1 and PSD-95, and neuronal network activity. Congruent with the neuronal phenotypes in mutant iNs, our transcriptomic analysis showed that the set of OTUD7A LoF-downregulated genes was enriched for those relating to synapse development and function and was associated with SZ and other neuropsychiatric disorders. These results suggest that OTUD7A LoF impairs synapse development and neuronal function in human neurons, providing mechanistic insight into the possible role of OTUD7A in driving neuropsychiatric phenotypes associated with the 15q13.3 deletion.
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