ArticleBMC endocrine disorders2021
A novel mutation of WFS1 gene leading to increase ER stress and cell apoptosis is associated an autosomal dominant form of Wolfram syndrome type 1.
Article in BMC endocrine disorders, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 23 citations in OpenAlex.
- Neutropenia Through Enhanced Neutrophil Apoptosis and Secondary Necrosis in Wolfram Syndrome 1Turkish journal of haematology : official journal of Turkish Society of Haematology · 2026Article
- The Genetic Landscape and Precision Medicine in Neonatal Diabetes Mellitus: From Molecular Mechanisms to Clinical Management.Current issues in molecular biology · 2026Review
- WFS1 Gene Mutation (c.2389G > A) Induces Immune Disorders by Promoting DC Maturation through Inhibition of TMEM176A.Inflammation · 2025Article
- Evolutionary trends in the emergence of skeletal cell types.Evolution letters · 2025Article
- Do wolframin, P-glycoprotein, and GRP78/BiP cooperate to alter the response of L1210 cells to endoplasmic reticulum stress or drug sensitivity?Cancer cell international · 2025Article
- [The analysis of gene screening results for common hereditary hearing loss in 2 102 pregnant women in Dali area].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2024Article
- SLC37A4, gene responsible for glycogen storage disease type 1b, regulates gingival epithelial barrier function via JAM1 expression.Scientific reports · 2024Article
- Disrupted Endoplasmic Reticulum CaBiology · 2024Review
- ISR inhibition reverses pancreatic β-cell failure in Wolfram syndrome models.Cell death and differentiation · 2024Article
- NovelFrontiers in genetics · 2024Article
- Neuronal Vulnerability of the Entorhinal Cortex to Tau Pathology in Alzheimer's Disease.British journal of biomedical science · 2024Review
- Neurosensory Affectation in Patients Affected by Wolfram Syndrome: Descriptive and Longitudinal Analysis.Healthcare (Basel, Switzerland) · 2023Article
- Neuroprotection from protein misfolding in cerebral hypoperfusion concurrent with metabolic syndrome. A translational perspective.Frontiers in neuroscience · 2023Review
- Paediatric Wolfram syndrome Type 1: should gonadal dysfunction be part of the diagnostic criteria?Frontiers in endocrinology · 2023Article
- Multidimensional analysis and therapeutic development using patient iPSC-derived disease models of Wolfram syndrome.JCI insight · 2022Article
- Case Report: HomozygousFrontiers in endocrinology · 2021Article
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5 authors at 1 institution in 1 country.
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Abstract
backgroundWolfram syndrome (WS) is a rare autosomal recessive disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy and deafness. Mutations in Wolfram syndrome 1 (WFS1) gene may cause dysregulated endoplasmic reticulum (ER)-stress and cell apoptosis, contributing to WS symptoms. The aim of this study was to identify the molecular etiology of a case of WS and to explore the functional consequence of the mutant WFS1 gene in vitro.
methodsA 27 years-old Chinese man was diagnosed as wolfram syndrome type 1 based on clinical data and laboratory data. DNA sequencing of WFS1 gene and mitochondrial m.3337G > A, m.3243A > G mutations were performed in the patient and his 4 family members. Functional analysis was performed to assessed the in vitro effect of the newly identified mutant. ER stress were evaluated by ER stress response element (ERSE)-luciferase assay. Cell apoptosis were performed by CCK-8, TUNEL staining and flow cytometric analysis.
resultsA novel heterozygous 10-base deletion (c. 2067_2076 del10, p.W690fsX706) was identified in the patient. In vitro studies showed that mutant p.W690fsX706 increased ERSE reporter activity in the presence or absence of thapsigargin instead of wild type WFS1. Knockdown of WFS1 activated the unfolded protein response (UPR) pathway and increased the cell apoptosis, which could not be restored by transfection with WFS1 mutant (p.W690fsX706) comparable to the wild type WFS1.
conclusionsA novel heterozygous mutation of WFS1 detected in the patient resulted in loss-of-function of wolframin, thereby inducing dysregulated ER stress signaling and cell apoptosis. These findings increase the spectrum of WFS1 gene mutations and broaden our insights into the roles of mutant WFS1 in the pathogenesis of WS.
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