ArticleBiological psychiatry2020
Synaptic Dysfunction in Human Neurons With Autism-Associated Deletions in PTCHD1-AS.
Article in Biological psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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54 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Mental health dished up-the use of iPSC models in neuropsychiatric research.Journal of neural transmission (Vienna, Austria : 1996) · 2020Pooled it
- Pathological Priming and Developmental Heterochrony as Organizing Concepts in Human iPSC Models of Autism Spectrum Disorder.Molecular neurobiology · 2026Review
- Disruption of major Ptchd1 isoforms causes autistic traits in social behavior and communication.Molecular psychiatry · 2026Article
- Hidden causal inference delineates dynamic lncRNA regulation in autism spectrum disorder.Briefings in bioinformatics · 2026Article
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- Regulatory Functions of Long Non-coding RNAs and Circular RNAs in the Molecular Pathogenesis of Autism Spectrum Disorder.Cellular and molecular neurobiology · 2025Review
- Analysis of neuronal activity impairment in iPSC-derived neurons from idiopathic autism patients.iScience · 2025Article
- Human Blood-Derived lncRNAs in Autism Spectrum Disorder.Biomolecules · 2025Review
- Genetic variants in DDX53 contribute to autism spectrum disorder associated with the Xp22.11 locus.American journal of human genetics · 2025Article
- Chromosome X-wide common variant association study in autism spectrum disorder.American journal of human genetics · 2025Article
- The Association Between Functional Variants in Long Non-coding RNAs and the Risk of Autism Spectrum Disorder Was Not Mediated by Gut Microbiota.Molecular neurobiology · 2025Article
- Combining Off-flow, a Nextflow-coded program, and whole genome sequencing reveals unintended genetic variation in CRISPR/Cas-edited iPSCs.Computational and structural biotechnology journal · 2024Article
- A deep learning model of dorsal and ventral visual streams for DVSD.Scientific reports · 2024Article
- An Inducible Luminescent System to Explore Parkinson's Disease-Associated Genes.International journal of molecular sciences · 2024Article
- Chromosome X-Wide Common Variant Association Study (XWAS) in Autism Spectrum Disorder.medRxiv : the preprint server for health sciences · 2024Article
- Loss-of-function mutation in DDX53 associated with hereditary spastic paraplegia-like disorder.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Recent Therapeutic Gene Editing Applications to Genetic Disorders.Current issues in molecular biology · 2024Review
- Structural rearrangements as a recurrent pathogenic mechanism for SETBP1 haploinsufficiency.Human genomics · 2024Article
- Distinctive In Vitro Phenotypes in iPSC-Derived Neurons From Patients With Gain- and Loss-of-FunctionThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- CRISPR-Cas9-generated PTCHD1 2489T>G stem cells recapitulate patient phenotype when undergoing neural induction.HGG advances · 2024Article
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe Xp22.11 locus that encompasses PTCHD1, DDX53, and the long noncoding RNA PTCHD1-AS is frequently disrupted in male subjects with autism spectrum disorder (ASD), but the functional consequences of these genetic risk factors for ASD are unknown.
methodsTo evaluate the functional consequences of PTCHD1 locus deletions, we generated induced pluripotent stem cells (iPSCs) from unaffected control subjects and 3 subjects with ASD with microdeletions affecting PTCHD1-AS/PTCHD1, PTCHD1-AS/DDX53, or PTCHD1-AS alone. Function of iPSC-derived cortical neurons was assessed using molecular approaches and electrophysiology. We also compiled novel and known genetic variants of the PTCHD1 locus to explore the roles of PTCHD1 and PTCHD1-AS in genetic risk for ASD and other neurodevelopmental disorders. Finally, genome editing was used to explore the functional consequences of deleting a single conserved exon of PTCHD1-AS.
resultsiPSC-derived neurons from subjects with ASD exhibited reduced miniature excitatory postsynaptic current frequency and N-methyl-D-aspartate receptor hypofunction. We found that 35 ASD-associated deletions mapping to the PTCHD1 locus disrupted exons of PTCHD1-AS. We also found a novel ASD-associated deletion of PTCHD1-AS exon 3 and showed that exon 3 loss altered PTCHD1-AS splicing without affecting expression of the neighboring PTCHD1 coding gene. Finally, targeted disruption of PTCHD1-AS exon 3 recapitulated diminished miniature excitatory postsynaptic current frequency, supporting a role for the long noncoding RNA in the etiology of ASD.
conclusionsOur genetic findings provide strong evidence that PTCHD1-AS deletions are risk factors for ASD, and human iPSC-derived neurons implicate these deletions in the neurophysiology of excitatory synapses and in ASD-associated synaptic impairment.
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