ArticlePloS one2019
Constitutive activation of mTORC1 signaling induced by biallelic loss-of-function mutations in SZT2 underlies a discernible neurodevelopmental disease.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Brain organoid models of SZT2-related disease reveal an overproduction of outer radial glial cells through mTORC1 activation.Scientific reports · 2026Article
- Bi-allelic KICS2 mutations impair KICSTOR complex-mediated mTORC1 regulation, causing intellectual disability and epilepsy.American journal of human genetics · 2025Article
- Customized targeted massively parallel sequencing enables the identification of novel pathogenic variants in Tunisian patients with developmental and epileptic encephalopathy.Epilepsia open · 2024Article
- Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes.Brain : a journal of neurology · 2023Article
- Genetic analysis of developmental and epileptic encephalopathy caused by novel biallelic SZT2 gene mutations in three Chinese Han infants: a case series and literature review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Review
- mTORC1 functional assay reveals SZT2 loss-of-function variants and a founder in-frame deletion.Brain : a journal of neurology · 2022Article
- A novel possible familial cause of epilepsy of infancy with migrating focal seizures related to SZT2 gene variant.Epilepsia open · 2021Article
- mTOR at the nexus of nutrition, growth, ageing and disease.Nature reviews. Molecular cell biology · 2020Review
- Identification, functional prediction, and key lncRNA verification of cold stress-related lncRNAs in rats liver.Scientific reports · 2020Article
- Mutational signature stratification of recurrent gliomas reveals distinct patterns of genomic traits.Neuro-oncology advancesArticle
- The Dysfunctional Gangway:Journal of pediatric neurosciencesArticle
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6 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
There have been increasing number of reports of SZT2-related neurological diseases, the main symptoms of which are epilepsy, developmental delay, macrocephaly and a dysmorphic corpus callosum. SZT2 functions as a regulator of mechanistic target of rapamycin complex 1 (mTORC1) signaling in cultured human cell lines and mouse tissues. However, it remains to be determined whether mutations in SZT2 in human patients alter mTORC1 signaling. In this study, we aimed to investigate the functional consequence of biallelic SZT2 variants in Epstein-Barr virus-induced lymphoblastoid cell lines (LCLs) established from two patients with a typical SZT2-related neurodevelopmental disease. Increased phosphorylation of S6 kinase and S6 was identified in patient-derived cell lines under amino acid-starved condition, suggestive of constitutive hyperactivation of mTORC1 signaling. This result was validated by constitutive lysosomal localization of mTOR in patients' LCLs. Furthermore, patients' LCLs display an excessive response to slight amino acid stimulation. Our data suggest the loss-of-function nature of SZT2 mutations in the patients, and consequent hyperactivation of mTORC1 signaling in response to both amino acid starvation and stimulation in their LCLs. By these functional analyses, the pathogenicity of newly identified SZT2 variants can be determined, allowing for more detailed characterization of genotype-phenotype correlations.
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