Natural history of patients with autosomal dominant WFS1 pathogenic variants associated with sensorineural hearing loss and optic atrophy
medRxiv [Preprint]. 2025 Feb 25:2025.02.23.25322342. doi: 10.1101/2025.02.23.25322342. ABSTRACT OBJECTIVE: Autosomal dominant pathogenic variants in the WFS1 gene can cause a broad spectrum of WFS1-related disorders. These disorders present with a range of phenotypic manifestations, including isolated low-frequency sensorineural hearing loss, optic nerve atrophy accompanied by low- to mid-frequency sensorineural hearing loss, isolated diabetes mellitus, and […]
GABA and GLP-1 receptor agonist combination therapy modifies diabetes and Langerhans islet cytoarchitecture in a rat model of Wolfram syndrome
Diabetol Metab Syndr. 2025 Mar 6;17(1):82. doi: 10.1186/s13098-025-01651-6. ABSTRACT BACKGROUND AND AIM: Wolfram syndrome (WS) is a rare autosomal disorder caused by WFS1 gene mutations, currently lacking approved treatments. Preclinical and clinical reports suggest that diabetes medications, such as glucagon-like peptide-1 receptor agonist (GLP1-RA), slow WS-related diabetes and neurodegeneration, improving patient outcomes. Gamma-aminobutyric acid (GABA) […]
Sodium valproate, a potential repurposed treatment for the neurodegeneration in Wolfram syndrome (TREATWOLFRAM): trial protocol for a pivotal multicentre, randomised double-blind controlled trial
BMJ Open. 2025 Feb 26;15(2):e091495. doi: 10.1136/bmjopen-2024-091495. ABSTRACT INTRODUCTION: Wolfram syndrome (WFS1-Spectrum Disorder) is an ultra-rare monogenic form of progressive neurodegeneration and diabetes mellitus. In common with most rare diseases, there are no therapies to slow or stop disease progression. Sodium valproate, an anticonvulsant with neuroprotective properties, is anticipated to mediate its effect via alteration […]
beta cell dedifferentiation, the underlying mechanism of diabetes in Wolfram syndrome
Sci Transl Med. 2025 Feb 19;17(786):eadp2332. doi: 10.1126/scitranslmed.adp2332. Epub 2025 Feb 19. ABSTRACT Insulin-dependent diabetes in patients with Wolfram syndrome (WS; OMIM 222300) has been linked to endoplasmic reticulum (ER) stress caused by WFS1 gene mutations. However, the pathological process of ER stress-associated β cell failure remains to be fully elucidated. Our results indicate loss […]
Identification of a pathogenic founder variant in the WFS1 gene that causes Wolfram syndrome in the Druze population
Front Pediatr. 2025 Jan 29;13:1525846. doi: 10.3389/fped.2025.1525846. eCollection 2025. ABSTRACT CONTEXT: Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disorder caused by pathogenic variants in the WFS1 gene. It is characterized by central diabetes insipidus, juvenile-onset diabetes mellitus (DM), optic atrophy (OA), and deafness. The natural history of WS is variable, even within the same […]
The Role of Visual Electrophysiology in Systemic Hereditary Syndromes
Int J Mol Sci. 2025 Jan 23;26(3):957. doi: 10.3390/ijms26030957. ABSTRACT Visual electrophysiology is a valuable tool for evaluating the visual system in various systemic syndromes. This review highlights its clinical application in a selection of syndromes associated with hearing loss, mitochondrial dysfunction, obesity, and other multisystem disorders. Techniques such as full-field electroretinography (ffERG), multifocal electroretinography […]
Do wolframin, P-glycoprotein, and GRP78/BiP cooperate to alter the response of L1210 cells to endoplasmic reticulum stress or drug sensitivity?
Cancer Cell Int. 2025 Feb 7;25(1):35. doi: 10.1186/s12935-025-03661-w. ABSTRACT In previous research, we revealed that murine leukemia cells L1210 with induced expression of P-glycoprotein (P-gp, a membrane drug transporter, product of the Abcb1 gene) are better able to withstand endoplasmic reticulum (ER) stress (ERS) than their P-gp negative counterparts. This was associated with increased GRP78/BiP […]
Prevalence and mechanisms of subacromial impingement in breast cancer patients after breast-conserving surgery and radiation therapy: a case-cohort study
Breast Cancer Res Treat. 2025 Feb;209(3):553-561. doi: 10.1007/s10549-024-07514-4. Epub 2024 Oct 21. ABSTRACT PURPOSE: Subacromial impingement is a painful shoulder disorder, which may be common after breast cancer treatment. A previous study showed a high prevalence after mastectomy but prevalence after conservatively treated patients is unknown. Impingement mechanisms in breast cancer survivors have not been […]
The Heterozygous p.A684V Variant in the WFS1 Gene Is a Mutational Hotspot Causing a Severe Hearing Loss Phenotype
Genes (Basel). 2025 Jan 6;16(1):57. doi: 10.3390/genes16010057. ABSTRACT BACKGROUND/OBJECTIVES: A heterozygous mutation in the WFS1 gene is responsible for autosomal dominant non-syndromic hearing loss (DFNA6/14/38) and Wolfram-like syndrome, which is characterized by bilateral sensorineural hearing loss with optic atrophy and/or diabetes mellitus. However, detailed clinical features for the patients with the heterozygous p.A684V variant remain […]
A Rare Case of Wolfram Syndrome Presenting With Tuberculous Meningitis: A Case Report
Clin Case Rep. 2025 Jan 16;13(1):e70116. doi: 10.1002/ccr3.70116. eCollection 2025 Jan. ABSTRACT Wolfram syndrome is an extremely rare condition composed of a tetrad of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. When concurrently presenting with another condition, such as tuberculous meningitis, the widespread range of resulting symptoms delays the establishment of diagnosis and treatment, […]