ArticleAmerican journal of human genetics2016
Biallelic Mutations of VAC14 in Pediatric-Onset Neurological Disease.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 61 citations in OpenAlex.
- Seasonal influences on DNA methylation at birth or at sampling time and their interaction with psychosis risk.Environmental epigenetics · 2026Article
- Bergeyella cardium variant induces a unique cytoplasmic vacuolization cell death floatptosis in macrophage.Cell discovery · 2025Article
- Novel VAC14 Variants Identified in a Patient with Striatonigral Degeneration and Prolonged Survival.Movement disorders clinical practice · 2025Article
- Expanding the Phenotypic Horizon of VAC14-Related Neurodegeneration.Movement disorders clinical practice · 2025Article
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- VAC14 oligomerization is essential for the function of the FAB1/PIKfyve-VAC14-FIG4 complex.Molecular biology of the cell · 2025Article
- Pediatric Genetic Dystonias: Current Diagnostic Approaches and Treatment Options.Life (Basel, Switzerland) · 2025Review
- Phosphoinositide Metabolism: Biochemistry, Physiology and Genetic Disorders.Journal of inherited metabolic disease · 2025Review
- Blepharoclonus - a novel phenotypic association with a VAC14 variant.Clinical parkinsonism & related disorders · 2025Article
- A Role of Inflammation in Charcot-Marie-Tooth Disorders-In a Perspective of Treatment?International journal of molecular sciences · 2024Review
- Osteogenesis imperfecta type 10 and the cellular scaffolds underlying common immunological diseases.Genes and immunity · 2024Review
- Exploring the phenotypic spectrum and osteopenia mechanisms in Yunis-Varón syndrome.Genetics in medicine open · 2024Article
- Functional genomics and small molecules in mitochondrial neurodevelopmental disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- The signalling lipid PI3,5POpen biology · 2023Article
- Altered phenotypes due to genetic interaction between the mouse phosphoinositide biosynthesis genes Fig4 and Pip4k2c.G3 (Bethesda, Md.) · 2023Article
- Unmistakable Truncal Dystonia Mistaken as Psychogenic: A Case Report of VAC14-Related Neurodegeneration.Movement disorders clinical practice · 2023Article
- The chloride antiporter CLCN7 is a modifier of lysosome dysfunction in FIG4 and VAC14 mutants.PLoS genetics · 2023Article
- Autophagic lysosome reformation in health and disease.Autophagy · 2023Review
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
- Roles of PIKfyve in multiple cellular pathways.Current opinion in cell biology · 2022Review
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
In the PI(3,5)P2 biosynthetic complex, the lipid kinase PIKFYVE and the phosphatase FIG4 are bound to the dimeric scaffold protein VAC14, which is composed of multiple heat-repeat domains. Mutations of FIG4 result in the inherited disorders Charcot-Marie-Tooth disease type 4J, Yunis-Varón syndrome, and polymicrogyria with seizures. We here describe inherited variants of VAC14 in two unrelated children with sudden onset of a progressive neurological disorder and regression of developmental milestones. Both children developed impaired movement with dystonia, became nonambulatory and nonverbal, and exhibited striatal abnormalities on MRI. A diagnosis of Leigh syndrome was rejected due to normal lactate profiles. Exome sequencing identified biallelic variants of VAC14 that were inherited from unaffected heterozygous parents in both families. Proband 1 inherited a splice-site variant that results in skipping of exon 13, p.Ile459Profs(∗)4 (not reported in public databases), and the missense variant p.Trp424Leu (reported in the ExAC database in a single heterozygote). Proband 2 inherited two missense variants in the dimerization domain of VAC14, p.Ala582Ser and p.Ser583Leu, that have not been previously reported. Cultured skin fibroblasts exhibited the accumulation of vacuoles that is characteristic of PI(3,5)P2 deficiency. Vacuolization of fibroblasts was rescued by transfection of wild-type VAC14 cDNA. The similar age of onset and neurological decline in the two unrelated children define a recessive disorder resulting from compound heterozygosity for deleterious variants of VAC14.
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