Mild Phenotype of Wolfram Syndrome Associated With a Common Pathogenic Variant Is Predicted by a Structural Model of Wolframin

Publication: neurology.org | Publication Date: March 19, 2021

Authors: Adi Wilf-Yarkoni, MD, MSc, Oded Shor, PhD, Avi Fellner, MD, Mark Andrew Hellmann, MD, Elon Pras, MD, Hagit Yonath, MD, Shiri Shkedi-Rafid, PhD, Lina Basel-Salmon, MD, PhD, Lili Bazak, PhD, Ruth Eliahou, MD, Lior Greenbaum, MD, PhD, Hadas Stiebel-Kalish, MD, Felix Benninger, MD and Yael Goldberg, MD

Abstract

Objective

To describe the WFS1 c.1672C>T; p.R558C missense variant, found in 1.34% of Ashkenazi Jews, that has a relatively mild phenotype and to use computational normal mode analysis (NMA) to explain the genotype-phenotype relationship. Read more

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Longitudinal Progression of Diabetes Mellitus in Wolfram Syndrome

Publication: diabetesjournals.org | Publication Date: June 1, 2020

Authors: Mary Katherine Ray, Tamara Hershey; Ling Chen, Neil H. White, Bess A. Marshall

Wolfram Syndrome (WFS) is a rare, genetic, neurodegenerative disorder with associated features of diabetes mellitus (DM), diabetes insipidus, deafness, and optic atrophy. In order to design intervention studies, concrete markers of disease progression are required. Read more

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Longitudinal Assessment of Neuroradiologic Features in Wolfram Syndrome

Publication: ajnr.org | Publication Date: October 29, 2020

Authors: A. Samara, H.M. Lugar, T. Hershey and J.S. Shimony

Abstract

Background and purpose: Wolfram syndrome is a rare genetic disease with characteristic brain involvement. We reviewed the brain MR images of patients with Wolfram syndrome to determine the frequency and characteristics of common neuroradiologic findings. Read more

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Liraglutide, 7,8-DHF and their co-treatment prevents loss of vision and cognitive decline in a Wolfram syndrome rat model

Publication: nature.com | Publication Date: January 26, 2021

Authors: Kadri Seppa, Toomas Jagomäe, Kaia Grete Kukker, Riin Reimets, Marko Pastak, Eero Vasar, Anton Terasmaa & Mario Plaas

Abstract

Wolfram syndrome (WS) is a monogenic progressive neurodegenerative disease and is characterized by various neurological symptoms, such as optic nerve atrophy, loss of vision, cognitive decline, memory impairment, and learning difficulties. Read more

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iPScells for treatment of WS

Publication: diabetesjournals.org | Publication Date: February 13, 2014

Authors: Fumihiko Urano

Wolfram syndrome is a rare autosomal recessive genetic disorder with clinical signs apparent in early childhood. This condition is characterized by childhood-onset diabetes, optic nerve atrophy, deafness, diabetes insipidus, and neurodegeneration, and it results in death in middle adulthood. Read more

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Hereditary Optic Neuropathies: Induced Pluripotent Stem Cell-Based 2D/3D Approaches

Abstract

Inherited optic neuropathies share visual impairment due to the degeneration of retinal ganglion cells (RGCs) as the hallmark of the disease. This group of genetic disorders are caused by mutations in nuclear genes or in the mitochondrial DNA (mtDNA). Read more

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GLP-1R agonists demonstrate potential to treat Wolfram syndrome in human preclinical models

Publication: Diabetologia | Publication Date: March 30, 2023

Authors: Vyron Gorgogietas, Bahareh Rajaei, Chae Heeyoung, Bruno J. Santacreu, Sandra Marín-Cañas, Paraskevi Salpea, Toshiaki Sawatani, Anyishai Musuaya, María N. Arroyo, Cristina Moreno-Castro, Khadija Benabdallah, Celine Demarez, Sanna Toivonen, Cristina Cosentino, Nathalie Pachera, Maria Lytrivi, Ying Cai, Lode Carnel, Cris Brown, Fumihiko Urano, Piero Marchetti, Patrick Gilon, Decio L. Eizirik, Miriam Cnop and Mariana Igoillo-Esteve

Abstract

Aims/hypothesis Wolfram syndrome is a rare autosomal recessive disorder caused by pathogenic variants in the WFS1 gene. It is characterised by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing loss and neurodegeneration. Considering the unmet treatment need for this orphan disease, this study aimed to evaluate the therapeutic potential of glucagon-like peptide 1 receptor (GLP-1R) agonists under wolframin (WFS1) deficiency with a particular focus on human beta cells and neurons.
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Gene Therapy Updates – Prime Editing

Publication: wolframsyndrome.wustl.edu | Publication Date: September 18, 2022

Authors: Fumihiko Urano

I have some exciting updates on our gene therapy development.

The root cause of Wolfram syndrome is pathogenic changes in the WFS1 gene. Therefore, correcting these changes in the WFS1 gene is the best way to treat Wolfram syndrome. Read more

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Function of WFS1 and WFS2 in the Central Nervous System: Implications for Wolfram Syndrome and Alzheimer’s disease

Publication: pubmed.ncbi.nlm.nih.gov | Publication Date: February 14, 2020

Authors: Liangping Li, Lalitha Venkataraman, Shuo Chen, Hongjun Fu

Abstract

L.P. Li, L. Venkataraman, S. Chen, and H.J. Fu. Function of WFS1 and WFS2 in the Central Nervous System: Implications for Wolfram Syndrome and Alzheimer’s Disease. NEUROSCI BIOBEHAV REVXXX-XXX,2020.-Wolfram syndrome (WS) is a rare monogenetic spectrum disorder characterized by insulin-dependent juvenile-onset diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing loss, progressive neurodegeneration, and a wide spectrum of psychiatric manifestations. Read more

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Endoplasmic-Reticulum Calcium Depletion and Disease

Publication: ncbi.nlm.nih.gov | Publication Date: January 7, 2016

Authors: Fumihiko Urano

Abstract

The endoplasmic reticulum (ER) as an intracellular Ca2+ store not only sets up cytosolic Ca2+ signals, but, among other functions, also assembles and folds newly synthesized proteins. Alterations in ER homeostasis, including severe Ca2+ depletion, are an upstream event in the pathophysiology of many diseases. Read more

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