Hereditary optic neuropathies (HON) often begin in adulthood. However, some of them can have an early onset. These may have specific clinical features and natural histories.
Retrospective study of ...HON patients with onset before the age of 14 years seen in a referral center. In addition to the age of onset, we evaluated the genetic etiology, visual acuity at 15 years, last best corrected visual acuity, optic disc appearance, visual field and extra-ophthalmological manifestations.
Forty-four patients (16 women) were included; i.e. 27.8% of all patients followed for HON. The mean age of onset was 8.5±3.3 years, with an onset earlier than 3 years in 5 patients. An etiology was not found in 8 patients. Of the remaining 36 patients, 12 had Leber's hereditary optic neuropathy (LHON), 11 had dominant optic atrophy, 12 had WS/WS-like syndrome, 2 had recessive optic atrophy and 1 had spastic paraplegia type 7. For 78 eyes of 40 patients (mean age 26.9±14.5 years), the mean last visual acuity was 0.80±0.33 LogMAR, with differences according to genetic forms. Visual acuity was less than or equal to counting fingers for 7 eyes (29.1%) of 4 WS/WS-like patients and one LHON patient.
Early onset NOH are not unusual. Their visual prognosis is as severe as adult onset NOH, with variations depending on the underlying genetic causes.
•Mice with a mutation in the Wolfram Syndrome gene Cisd2, display sonic vocalizations.•Mutants display hypoactivity across several behavioral assays.•Cisd2 mutants have elevated ...corticosterone.•Mutant mice exhibit lower prepulse inhibition.•Unlike Wolfram Syndrome patients, mutant mice do not have impaired glucose tolerance.
Wolfram syndrome (WFS) is a rare autosomal recessive disorder characterized by diabetes mellitus and insipidus, progressive optic atrophy and sensorineural deafness. An increased incidence of psychiatric disorders has also been reported in WFS patients. There are two subtypes of WFS. Type 1 (WFS1) is caused by mutations in the WFS1 gene and type 2 (WFS2) results from mutations in the CISD2 gene. Existing Wfs1 knockout mice exhibit many WFS1 cardinal symptoms including diabetic nephropathy, metabolic disruptions and optic atrophy. Far fewer studies have examined loss of Cisd2 function in mice. We identified B6.DDY-Cisd2m1Lmt, a mouse model with a spontaneous mutation in the Cisd2 gene. B6.DDY-Cisd2m1Lmt mice were initially identified based on the presence of audible sonic vocalizations as well as decreased body size and weight compared to unaffected wildtype littermates. Although Wfs1 knockout mice have been characterized for numerous behavioral phenotypes, similar studies have been lacking for Cisd2 mutant mice. We tested B6.DDY-Cisd2m1Lmt mice in a battery of behavioral assays that model phenotypes related to neurological and psychiatric disorders including anxiety, sensorimotor gating, stress response, social interaction and learning and memory. B6.DDY-Cisd2m1Lmt mice displayed hypoactivity across several behavioral tests, exhibited increased stress response and had deficits in spatial learning and memory and sensorimotor gating compared to wildtype littermates. Our data indicate that the B6.DDY-Cisd2m1Lmt mouse strain is a useful model to investigate potential mechanisms underlying the neurological and psychiatric symptoms observed in WFS.
In the pursuit of materials with exceptional mechanical properties, a machine-learning model is developed to direct the synthetic efforts toward compounds with high hardness by predicting the elastic ...moduli as a proxy. This approach screens 118 287 compounds compiled in crystal structure databases for the materials with the highest bulk and shear moduli determined by support vector machine regression. Following these models, a ternary rhenium tungsten carbide and a quaternary molybdenum tungsten borocarbide are selected and synthesized at ambient pressure. High-pressure diamond anvil cell measurements corroborate the machine-learning prediction of the bulk modulus with less than 10% error, as well as confirm the ultraincompressible nature of both compounds. Subsequent Vickers microhardness measurements reveal that each compound also has an extremely high hardness exceeding the superhard threshold of 40 GPa at low loads (0.49 N). These results show the effectiveness of materials development through state-of-the-art machine-learning techniques by identifying functional inorganic materials.
Wolfram syndrome (WS) is a rare genetic disorder typically characterized by juvenile onset diabetes mellitus, optic atrophy, hearing loss, diabetes insipidus, and neurodegeneration. There would be a ...high index of clinical suspicion for WS when clinical manifestations of type 1 diabetes and optic atrophy present together. Genetic analysis is often required to confirm the diagnosis. We describe a pair of Chinese siblings diagnosed with WS at ages 20 and 24 years, respectively. DNA sequencing of the WFS1 gene which encodes for Wolframin ER Transmembrane Glycoprotein identified a heterozygous nonsense variant NM_006005.3: c.1999C>T p.(Gln667*) and a heterozygous missense variant c.2170C>T p.(Pro724Ser) in exon 8 of the gene for both siblings. There is no curative treatment for WS and management of this debilitating disease is aimed at treating individual clinical manifestations, slowing disease progression, and improving quality of life. Treatment with liraglutide, a glucagon-like-peptide-1 receptor agonist, and tauroursodeoxycholic acid was started for the younger sibling, the proband. There was reduction in insulin requirements and improvement in glycemic control. The other sibling was not offered liraglutide due to her complex treatment regimen for end-organ failure. Genetic testing is a valuable tool to detect WS early to allow precise and prompt diagnosis, thereby facilitating the coordinated care from a multidisciplinary team of clinicians.
Natural photosynthesis is a solar light-driven process utilized by plants to convert CO2 and water into carbohydrate molecules. The goal of artificial photosynthesis is the reduction of CO2 directly ...from air into high purity value-added products at atmospheric pressure. However, its realization, combined with deep mechanism investigation, is a huge challenge. Herein, we demonstrate that hexagonal tungsten bronze M0.33WO3 (M = K, Rb, Cs) series with {010} facets, prepared by a peculiar “water-controllable releasing” solvothermal method, showed excellent full spectrum (UV, visible, and NIR lights)-induced photocatalytic CO2 reduction performance directly from the air at ambient pressure. Particularly, after 4 h near-infrared light irradiation, ca. 4.32% CO2 in the air could be converted into CH3OH with 98.35% selectivity for Rb0.33WO3. The experiments and theoretical calculations unveiled that the introduced alkali metal atom occupied the tunnel of hexagonal structure and donated more free electrons to reconstruct the electronic structure of M0.33WO3, which can enhance the polaron transition, modify the energy band structure, selectively adsorb CO2 rather than O2 from the air, decrease the activation energy of CO2 reaction, and finally make the effective CO2 reduction in the air a reality. This work may provide a new possibility for the practical application of artificial photosynthesis.
Mitochondrial dysfunction involving mitochondria-associated ER membrane (MAM) dysregulation is implicated in the pathogenesis of late-onset neurodegenerative diseases, but understanding is limited ...for rare early-onset conditions. Loss of the MAM-resident protein WFS1 causes Wolfram syndrome (WS), a rare early-onset neurodegenerative disease that has been linked to mitochondrial abnormalities. Here we demonstrate mitochondrial dysfunction in human induced pluripotent stem cell-derived neuronal cells of WS patients. VDAC1 is identified to interact with WFS1, whereas loss of this interaction in WS cells could compromise mitochondrial function. Restoring WFS1 levels in WS cells reinstates WFS1-VDAC1 interaction, which correlates with an increase in MAMs and mitochondrial network that could positively affect mitochondrial function. Genetic rescue by WFS1 overexpression or pharmacological agents modulating mitochondrial function improves the viability and bioenergetics of WS neurons. Our data implicate a role of WFS1 in regulating mitochondrial functionality and highlight a therapeutic intervention for WS and related rare diseases with mitochondrial defects.
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•Wolfram syndrome patient-derived neuronal cells exhibit mitochondrial dysfunction•Loss of WFS1 interaction with VDAC1 could potentially affect mitochondrial function•Mitochondrial and cell death phenotypes are rescued by genetic correction•Pharmacological agents rescue mitochondrial defects and improve neuronal viability
In this article, Sarkar and colleagues describe mitochondrial dysfunction in neuronal cells generated from patient-derived iPSCs of Wolfram syndrome, a rare early-onset neurodegenerative disorder. Genetic rescue by WFS1 restoration or chemical rescue by drugs modulating mitochondrial function improves the bioenergetics and viability of Wolfram syndrome patient neurons, thus providing insights for therapeutic intervention.
The story of the Grail, usually identified as some kind of mystical vessel, has gripped the imaginations of millions since it first appeared in several medieval romances. Of these, Wolfram von ...Eschenbach's Middle High German Parzival (c. 1210) is generally recognized as the most complex and beautiful. Strangely, in Parzival, the Grail is identified as a stone rather than a cup or dish. This oddity is usually seen as just another mystery, further evidence of the difficulty of discerning the true sources of the Grail legend. This book seeks to illuminate this mystery and to enable a far better appreciation of Wolfram's insight into the nature of the Grail and its relationship to the Crusades. The Grail, container of the sacred body and blood of Christ, Wolfram was saying, was where God said it would be: on the altar at the consecration of the Mass. Wolfram's “sacred stone” was none other than a consecrated altar, precious by virtue of the sacrament but also, this book argues, by virtue of the material from which it was made: a green gem, one of the precious stones associated with the rivers of Paradise. The book explores what it signifies for the Grail to be a translucent gemstone and an altar made portable only by a woman. Wolfram's stone is a sacramental reference to the stone the Crusaders fought to obtain — the Holy Sepulchre. Parzival, the book states, was intended as an argument against continued efforts by Latin Christians to recover the Holy Sepulcher in Jerusalem by force of arms. In Wolfram's story, warring Christian and Muslim brothers are brought together in peace by the power of Wolfram's Holy Grail.
Wolfram-like syndrome: a case report Zhu, B X; Zhang, L; Wang, H Y ...
Chung-hua yen k'o tsa chih,
2024-Feb-11, Letnik:
60, Številka:
2
Journal Article
Different from classical autosomal recessive Wolfram syndrome, Wolfram-like syndrome is an autosomal dominant disorder caused by a heterozygous mutation in the WFS1 gene. In this case, a 7-year-old ...male child presented to the eye clinic due to vision loss that could not be corrected, discovered during a routine examination. The child had experienced hearing impairment since early childhood, leading to cochlear implantation. Ophthalmic examination revealed optic disc atrophy in both eyes. Optical coherence tomography imaging demonstrated a distinctive thickening of the outer plexiform layer with abnormal layering, characteristic of a single mutation in the WFS1 gene. Subsequent genetic testing identified a de novo heterozygous missense mutation c.2051C>T (p.A684V) in the WFS1 gene, which ultimately led to the diagnosis of Wolfram-like syndrome.
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