Clinical Trials for Wolfram Syndrome Neurodegeneration: Novel Design, Endpoints, and Analysis Models
medRxiv [Preprint]. 2024 Sep 11:2024.09.10.24313426. doi: 10.1101/2024.09.10.24313426. ABSTRACT OBJECTIVE: Wolfram syndrome, an ultra-rare condition, currently lacks effective treatment options. The rarity of this disease presents significant challenges in conducting clinical trials, particularly in achieving sufficient statistical power (e.g., 80%). The objective of this study is to propose a novel clinical trial design based on real-world […]
Early presentation of urological abnormalities in a case of Wolfram syndrome
BMJ Case Rep. 2024 Sep 20;17(9):e260822. doi: 10.1136/bcr-2024-260822. ABSTRACT Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disorder characterised by arginine vasopressin deficiency (AVP-D), juvenile type 1 diabetes mellitus (DM), optic atrophy (OA) and deafness. We describe an early adolescent female child being managed initially as a case of juvenile type 1 DM presented […]
Images in sleep medicine sleep-disordered breathing in Wolfram’s syndrome – A near-fatal event
Sleep Med. 2024 Sep 12;124:106-109. doi: 10.1016/j.sleep.2024.09.012. Online ahead of print. ABSTRACT Wolfram syndrome (WS) is a rare autosomal-recessive genetic disorder. The authors report a case of a patient with WS and undiagnosed/untreated obstructive sleep apnea (OSA) associated with prolonged periods of apnea and hypopnea and nocturnal hypoxemia, which may have predisposed him to the […]
Endoplasmic reticulum-mitochondria lockdown in Wolfram syndrome
Cell Calcium. 2024 Sep 12;124:102955. doi: 10.1016/j.ceca.2024.102955. Online ahead of print. ABSTRACT Wolfram syndrome (WS) is an incurable autosomal recessive disorder originally described as a mitochondriopathy. In a recent work, Liiv and colleagues found that an impaired endoplasmic reticulum (ER)-to-mitochondria calcium shuttling underlies mitochondrial dysfunction in WS models. PMID:39278009 | DOI:10.1016/j.ceca.2024.102955
Discovery of a TRMT10A mutation in a case of atypical diabetes: case report
Diabetes Metab. 2024 Sep 5:101572. doi: 10.1016/j.diabet.2024.101572. Online ahead of print. ABSTRACT It is notable that monogenic forms of diabetes are exceedingly uncommon, with only 28 genes thus far identified. Such conditions frequently result in the dysfunction of pancreatic cells responsible for insulin production. Mutation in the TRMT10A gene leads to a rare genetic disease […]
Novel WFS1 variants are associated with different diabetes phenotypes
Front Genet. 2024 Aug 16;15:1433060. doi: 10.3389/fgene.2024.1433060. eCollection 2024. ABSTRACT BACKGROUND: The WFS1 gene encodes the protein wolframin, which is crucial for maintaining endoplasmic reticulum homeostasis. Variants in this gene are predominantly associated with Wolfram syndrome and have been implicated in other disorders such as diabetes mellitus and psychiatric diseases, which increases the rate of […]
Wolfram Syndrome 1: A Neuropsychiatric Perspective on a Rare Disease
Genes (Basel). 2024 Jul 25;15(8):984. doi: 10.3390/genes15080984. ABSTRACT Wolfram syndrome 1 (WS1) is an uncommon autosomal recessive neurological disorder that is characterized by diabetes insipidus, early-onset non-autoimmune diabetes mellitus, optic atrophy, and deafness (DIDMOAD). Other clinical manifestations are neuropsychiatric symptoms, urinary tract alterations, and endocrinological disorders. The rapid clinical course of WS1 results in death […]
Clinical Characteristics and Audiological Profiles of Patients with Pathogenic Variants of WFS1
J Clin Med. 2024 Aug 16;13(16):4851. doi: 10.3390/jcm13164851. ABSTRACT Background: Mutations in Wolfram syndrome 1 (WFS1) cause Wolfram syndrome and autosomal dominant non-syndromic hearing loss DFNA6/14/38. To date, more than 300 pathogenic variants of WFS1 have been identified. Generally, the audiological phenotype of Wolfram syndrome or DFNA6/14/38 is characterized by low-frequency hearing loss; however, this […]
A deep phenotyping study in mouse and iPSC models to understand the role of oligodendroglia in optic neuropathy in Wolfram syndrome
Acta Neuropathol Commun. 2024 Aug 28;12(1):140. doi: 10.1186/s40478-024-01851-7. ABSTRACT Wolfram syndrome (WS) is a rare childhood disease characterized by diabetes mellitus, diabetes insipidus, blindness, deafness, neurodegeneration and eventually early death, due to autosomal recessive mutations in the WFS1 (and WFS2) gene. While it is categorized as a neurodegenerative disease, it is increasingly becoming clear that […]
Immunoinformatic-based drug design utilizing hesperetin to target CISD2 activation for liver aging in humans
Biogerontology. 2024 Aug 28. doi: 10.1007/s10522-024-10130-w. Online ahead of print. ABSTRACT The CISD protein family, consisting of CISD1, CISD2, and CISD3, encodes proteins that feature CDGSH iron-sulfur domains crucial for cellular functions and share a common 2Fe-2S domain. CISD2, which is pivotal in cells, regulates intracellular calcium levels, maintains the endoplasmic reticulum and mitochondrial function, […]