ArticleBiological psychiatry2022
PDZD8 Disruption Causes Cognitive Impairment in Humans, Mice, and Fruit Flies.
Article in Biological psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Inter-Organelle Membrane Contact Sites as Physiological Regulatory Hubs in the Brain: From Neurons to Glial Cells.Biomolecules · 2026Review
- Mitochondrial dynamics in neurodevelopment and neurodevelopmental disorders.Nature reviews. Neuroscience · 2026Review
- Mitochondria-ER contact sites in neurological disorders.Animal cells and systems · 2026Review
- PDZD8 Dysregulation Mediates RVLM Neuronal Hyperexcitation Via Activation of CaMolecular neurobiology · 2025Article
- LYVAC/PDZD8 is a lysosomal vacuolator.Science (New York, N.Y.) · 2025Article
- PDZD8 promotes autophagy at ER-lysosome membrane contact sites to regulate activity-dependent synaptic growth.Cell reports · 2025Article
- Mitochondrial complexity is regulated at ER-mitochondria contact sites via PDZD8-FKBP8 tethering.Nature communications · 2025Article
- Autistic behavior is a common outcome of biallelic disruption of PDZD8 in humans and mice.Molecular autism · 2025Article
- Pathogenic contribution of cholesteryl ester accumulation in the brain to neurodegenerative disorders.Neural regeneration research · 2024Article
- Protective effect of PDE4B subtype-specific inhibition in an App knock-in mouse model for Alzheimer's disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Rare variants analyses suggest novel cleft genes in the African population.Scientific reports · 2024Article
- Rare Variants Analyses Suggest Novel Cleft Genes in the African Population.Research square · 2024Article
- Lysosomes in senescence and aging.EMBO reports · 2023Review
- Review
- PDZD8-deficient mice manifest behavioral abnormalities related to emotion, cognition, and adaptation due to dyslipidemia in the brain.Molecular brain · 2023Article
- PDZD8-deficient mice accumulate cholesteryl esters in the brain as a result of impaired lipophagy.iScience · 2022Article
- Decreasing pdzd8-mediated mito-ER contacts improves organismal fitness and mitigates AβLife science alliance · 2022Article
- Recent Advances on Synaptotagmin-Like Mitochondrial-Lipid Binding Protein Domain Containing Lipid Transfer Proteins.Contact (Thousand Oaks (Ventura County, Calif.))Review
Corrections and comments
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Authors and funding
25 authors at 10 institutions in 6 countries.
Funding
Abstract
backgroundThe discovery of coding variants in genes that confer risk of intellectual disability (ID) is an important step toward understanding the pathophysiology of this common developmental disability.
methodsHomozygosity mapping, whole-exome sequencing, and cosegregation analyses were used to identify gene variants responsible for syndromic ID with autistic features in two independent consanguineous families from the Arabian Peninsula. For in vivo functional studies of the implicated gene's function in cognition, Drosophila melanogaster and mice with targeted interference of the orthologous gene were used. Behavioral, electrophysiological, and structural magnetic resonance imaging analyses were conducted for phenotypic testing.
resultsHomozygous premature termination codons in PDZD8, encoding an endoplasmic reticulum-anchored lipid transfer protein, showed cosegregation with syndromic ID in both families. Drosophila melanogaster with knockdown of the PDZD8 ortholog exhibited impaired long-term courtship-based memory. Mice homozygous for a premature termination codon in Pdzd8 exhibited brain structural, hippocampal spatial memory, and synaptic plasticity deficits.
conclusionsThese data demonstrate the involvement of homozygous loss-of-function mutations in PDZD8 in a neurodevelopmental cognitive disorder. Model organisms with manipulation of the orthologous gene replicate aspects of the human phenotype and suggest plausible pathophysiological mechanisms centered on disrupted brain development and synaptic function. These findings are thus consistent with accruing evidence that synaptic defects are a common denominator of ID and other neurodevelopmental conditions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.