ArticleHuman molecular genetics2021
Novel mutations in the WFS1 gene are associated with Wolfram syndrome and systemic inflammation.
Article in Human molecular genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- A phase Ib/IIa clinical trial of dantrolene sodium in patients with Wolfram syndrome.JCI insight · 2021Trial
- Functional characterization of porcine septin12 and its role in male reproduction.Animal bioscience · 2026Article
- Genotype-Based Severity Scoring System in Wolfram Syndrome: Correlation with Onset of Cardinal Symptoms andmedRxiv : the preprint server for health sciences · 2026Article
- The Genetic Landscape and Precision Medicine in Neonatal Diabetes Mellitus: From Molecular Mechanisms to Clinical Management.Current issues in molecular biology · 2026Review
- Genotype-based severity scoring system in Wolfram Syndrome: correlation with onset of cardinal symptoms andFrontiers in genetics · 2026Article
- WFS1 Gene Mutation (c.2389G > A) Induces Immune Disorders by Promoting DC Maturation through Inhibition of TMEM176A.Inflammation · 2025Article
- Circadian Rhythm and Psychiatric Features in Wolfram Syndrome: Toward Chrono Diagnosis and Chronotherapy.Diagnostics (Basel, Switzerland) · 2025Article
- Article
- SID/SIEDP expert consensus on optimizing clinical strategies for early detection and management of wolfram syndrome.Journal of endocrinological investigation · 2025Review
- Expanding the spectrum of white matter abnormalities in Wolfram syndrome: a retrospective review.Frontiers in neurology · 2025Article
- Proteome-Wide Mapping of Artesunate Targets Reveals Enrichment of the Ubiquitin-Proteasome System.Drug design, development and therapy · 2025Article
- A WFS1 variant disrupting acceptor splice site uncovers the impact of alternative splicing on beta cell apoptosis in a patient with Wolfram syndrome.Diabetologia · 2025Article
- A deep phenotyping study in mouse and iPSC models to understand the role of oligodendroglia in optic neuropathy in Wolfram syndrome.Acta neuropathologica communications · 2024Article
- Cardiac Wolframinopathies: A Case Report of Myocarditis and a Literature Review of Cardiac Involvement in Wolfram Syndrome 1.Journal of clinical medicine · 2024Review
- Comprehensive overview of disease models for Wolfram syndrome: toward effective treatments.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Review
- Inflammation and olfactory loss are associated with at least 139 medical conditions.Frontiers in molecular neuroscience · 2024Article
- Single-cell transcriptomics reveals a role for pancreatic duct cells as potential mediators of inflammation in diabetes mellitus.Frontiers in immunology · 2024Article
- Mutation analysis of pathogenic non-synonymous single nucleotide polymorphisms (nsSNPs) in WFS1 gene through computational approaches.Scientific reports · 2023Article
- Neuroprotection from protein misfolding in cerebral hypoperfusion concurrent with metabolic syndrome. A translational perspective.Frontiers in neuroscience · 2023Review
- Genotype and clinical characteristics of patients with Wolfram syndrome and WFS1-related disorders.Frontiers in genetics · 2023Article
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the WFS1 gene, encoding wolframin (WFS1), cause endoplasmic reticulum (ER) stress and are associated with a rare autosomal-recessive disorder known as Wolfram syndrome (WS). WS is clinically characterized by childhood-onset diabetes mellitus, optic atrophy, deafness, diabetes insipidus and neurological signs. We identified two novel WFS1 mutations in a patient with WS, namely, c.316-1G > A (in intron 3) and c.757A > T (in exon 7). Both mutations, located in the N-terminal region of the protein, were predicted to generate a truncated and inactive form of WFS1. We found that although the WFS1 protein was not expressed in peripheral blood mononuclear cells (PBMCs) of the proband, no constitutive ER stress activation could be detected in those cells. In contrast, WS proband's PBMCs produced very high levels of proinflammatory cytokines (i.e. TNF-α, IL-1β, and IL-6) in the absence of any stimulus. WFS1 silencing in PBMCs from control subjects by means of small RNA interference also induced a pronounced proinflammatory cytokine profile. The same cytokines were also significantly higher in sera from the WS patient as compared to matched healthy controls. Moreover, the chronic inflammatory state was associated with a dominance of proinflammatory T helper 17 (Th17)-type cells over regulatory T (Treg) lymphocytes in the WS PBMCs. The identification of a state of systemic chronic inflammation associated with WFS1 deficiency may pave the way to innovative and personalized therapeutic interventions in WS.
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