Clinical manifestations of dual-gene variants involving ABCA4 in retinal dystrophies
BMC Ophthalmol. 2025 Apr 23;25(1):239. doi: 10.1186/s12886-025-04048-1. ABSTRACT BACKGROUND: This study investigates the clinical manifestations of inherited retinal diseases (IRD) associated with dual-gene variant constellations involving biallelic ABCA4 variants. METHODS: We assess four cases for their unique phenotypic outcomes due to biallelic ABCA4 variants and additional genotypes in CACNA1F, IMPG1, HK1 and MYO7A, respectively. RESULTS: […]
Improving mitochondria-associated endoplasmic reticulum membranes integrity as converging therapeutic strategy for rare neurodegenerative diseases and cancer
Biochim Biophys Acta Mol Cell Res. 2025 Apr 9:119954. doi: 10.1016/j.bbamcr.2025.119954. Online ahead of print. ABSTRACT Membrane contact sites harbor a distinct set of proteins with varying biological functions, thereby emerging as hubs for localized signaling nanodomains underlying adequate cell function. Here, we will focus on mitochondria-associated endoplasmic reticulum membranes (MAMs), which serve as hotspots […]
Liraglutide treatment reverses unconventional cellular defects in induced pluripotent stem cell-derived β cells harboring a partially functional WFS1 variant
Diabetes. 2025 Apr 9:db240720. doi: 10.2337/db24-0720. Online ahead of print. ABSTRACT Wolfram Syndrome 1 (WS1) is a rare genetic disorder caused by WFS1 variants that disrupt Wolframin, an endoplasmic reticulum-associated protein essential for cellular stress responses, Ca2+ homeostasis, and autophagy. Here, we investigated how the c.316-1G>A and c.757A>T WFS1 mutations, which yield partially functional Wolframin, […]
Wolfram syndrome 2 gene (CISD2) deficiency disrupts Ca(2+)-mediated insulin secretion in beta-cells
Mol Metab. 2025 Apr 4:102140. doi: 10.1016/j.molmet.2025.102140. Online ahead of print. ABSTRACT OBJECTIVES: Diabetes, characterized by childhood-onset, autoantibody-negativity and insulin-deficiency, is a major manifestation of Wolfram syndrome 2 (WFS2), which is caused by recessive mutations of CISD2. Nevertheless, the mechanism underlying β-cell dysfunction in WFS2 remains elusive. Here we delineate the essential role of CISD2 […]
Reciprocal rescue of Wolfram syndrome by two causative genes
EMBO Rep. 2025 Apr 3. doi: 10.1038/s44319-025-00436-2. Online ahead of print. ABSTRACT Wolfram syndrome (WS) is marked by juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. The causative genes, WFS1 and CISD2, correspond to WS types 1 and 2, respectively. Here, we establish their mutual indispensability for inositol 1,4,5-triphosphate receptor (IP3R) activity, […]
Atypical Forms of Diabetes
2025 Mar 10. In: Feingold KR, Ahmed SF, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Muzumdar R, Purnell J, […]
Nuclear factor erythroid 2-related factor improves depression and cognitive dysfunction in rats with ischemic stroke by mediating wolfram syndrome 1
Brain Res. 2025 Mar 16:149572. doi: 10.1016/j.brainres.2025.149572. Online ahead of print. ABSTRACT OBJECTIVE: This research aims to investigate the molecular mechanism of nuclear factor erythroid 2-related factor (Nrf2) in improving post-stroke depression and cognitive impairment (PSDCI) by mediating wolfram syndrome 1 (Wfs1). METHODS: PSDCI rat model was established through middle cerebral artery occlusion (MCAO) and […]
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 […]