ArticleBrain : a journal of neurology2019
A mutation in the major autophagy gene, WIPI2, associated with global developmental abnormalities.
Article in Brain : a journal of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Emerging roles of ATG7 in human health and disease.EMBO molecular medicine · 2021Pooled it
- Synaptic Proteostasis in Health and Disease.Journal of neurochemistry · 2026Review
- Roles of autophagy in brain homeostasis and disease.Nature neuroscience · 2026Review
- A GABARAP-PtdIns3K-C1 positive feedback loop at the heart of the phagophore nucleation.Nature communications · 2026Article
- Autophagic Pathway on GABARAP Involved in GABANeurochemical research · 2026Review
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- Inhibition of histone deacetylase 6 activity mitigates neurological impairment and post-hemorrhagic hydrocephalus after intraventricular hemorrhage by modulating pyroptosis and autophagy pathways.Fluids and barriers of the CNS · 2025Article
- Classification of Brain Magnetic Resonance Imaging Abnormalities and Spectrum of Neurological Findings in a Cohort with Copy Number Variation-Related Disorders.Molecular syndromology · 2025Article
- Impact of Larval Sertraline Exposure on Alternative Splicing in Neural Tissue of AdultInternational journal of molecular sciences · 2025Article
- Mitochondrial dysfunction, cause or consequence in neurodegenerative diseases?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Explore autophagy-related lncRNA-miRNA-mRNA ceRNA networks for diagnosis of early-onset schizophrenia through transcriptome analysis.Frontiers in psychiatry · 2025Article
- Mechanisms of autophagy-lysosome dysfunction in neurodegenerative diseases.Nature reviews. Molecular cell biology · 2024Review
- C16ORF70/MYTHO promotes healthy aging in C.elegans and prevents cellular senescence in mammals.The Journal of clinical investigation · 2024Article
- Review
- Comprehensive analysis of autophagic functions of WIPI family proteins and their implications for the pathogenesis of β-propeller associated neurodegeneration.Human molecular genetics · 2023Article
- Autophagy genes in biology and disease.Nature reviews. Genetics · 2023Review
- ATG16L1 adopts a dual-binding site mode to interact with WIPI2b in autophagy.Science advances · 2023Article
- Autophagopathies: from autophagy gene polymorphisms to precision medicine for human diseases.Autophagy · 2022Article
- Mutations inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
Corrections and comments
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Authors and funding
15 authors at 10 institutions in 4 countries.
Funding
Abstract
We describe a large consanguineous pedigree from a remote area of Northern Pakistan, with a complex developmental disorder associated with wide-ranging symptoms, including mental retardation, speech and language impairment and other neurological, psychiatric, skeletal and cardiac abnormalities. We initially carried out a genetic study using the HumanCytoSNP-12 v2.1 Illumina gene chip on nine family members and identified a single region of homozygosity shared amongst four affected individuals on chromosome 7p22 (positions 3059377-5478971). We performed whole-exome sequencing on two affected individuals from two separate branches of the extended pedigree and identified a novel nonsynonymous homozygous mutation in exon 9 of the WIPI2 (WD-repeat protein interacting with phosphoinositide 2) gene at position 5265458 (c.G745A;pV249M). WIPI2 plays a critical role in autophagy, an evolutionary conserved cellular pathway implicated in a growing number of medical conditions. The mutation is situated in a highly conserved and critically important region of WIPI2, responsible for binding PI(3)P and PI(3,5)P2, an essential requirement for autophagy to proceed. The mutation is absent in all public databases, is predicted to be damaging and segregates with the disease phenotype. We performed functional studies in vitro to determine the potential effects of the mutation on downstream pathways leading to autophagosome assembly. Binding of the V231M mutant of WIPI2b to ATG16L1 (as well as ATG5-12) is significantly reduced in GFP pull-down experiments, and fibroblasts derived from the patients show reduced WIPI2 puncta, reduced LC3 lipidation and reduced autophagic flux.
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Registered trials
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