Previously unreported abnormalities in Wolfram Syndrome Type 2

Aktürk, Halis Kaan; Yasa, Seda

doi:10.18544/pedm-23.02.0081

Cited by 8 publications

(5 citation statements)

References 13 publications

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“…A recent case report described asymptomatic hypoparathyroidism, osteomalacia and growth hormone (GH) deficiency in two siblings who are affected by WS2 whose diagnosis was not supported by a genetic investigation [ 25 ]. Except for these sporadic cases, no other endocrinological abnormalities are reported among the WS2 patients who are described in the literature.…”

Section: Resultsmentioning

confidence: 99%

Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum

Rosanio

Candia

Occhiati

et al. 2022

IJERPH

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Background: Wolfram syndrome (WS) is a rare autosomal recessive disorder that is characterized by the presence of diabetes mellitus, optic atrophy and hearing loss, all of which are crucial elements for the diagnosis. WS is variably associated with diabetes insipidus, neurological disorders, urinary tract anomalies, endocrine dysfunctions and many other systemic manifestations. Since Wolfram and Wagener first described WS in 1938, new phenotypic/genotypic variants of the syndrome have been observed and the clinical picture has been significantly enriched. To date, two main subtypes of WS that associated with two different mutations are known: WS type 1 (WS1), caused by the mutation of the wolframine gene (WS1; 606201), and WS type 2 (WS2), caused by the mutation of the CISD2 gene (WS2; 604928). Methods: A systematic review of the literature was describe the phenotypic characteristics of WS2 in order to highlight the key elements that differentiate it from the classic form. Conclusion: WS2 is the rarest and most recently identified subtype of WS; its clinical picture is partially overlapping with that of WS1, from which it traditionally differs by the absence of diabetes insipidus and the presence of greater bleeding tendency and peptic ulcers.

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Section: Resultsmentioning

confidence: 99%

Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum

Rosanio

Candia

Occhiati

et al. 2022

IJERPH

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“…Two additional unrelated new cases of WFS-T2 were further reported at 2017 [50,86]. Unfortunately, there was no genetic analysis to confirm these cases [86].…”

Section: Ivc Naf-1 and Wolfram Syndrome Type 2 (Wfs-t2)mentioning

confidence: 99%

“…Two additional unrelated new cases of WFS-T2 were further reported at 2017 [50,86]. Unfortunately, there was no genetic analysis to confirm these cases [86]. In 2019 a homozygous deletion of two nucleotides TG c.272-273del was reported in a Chinese family.…”

Section: Ivc Naf-1 and Wolfram Syndrome Type 2 (Wfs-t2)mentioning

confidence: 99%

The balancing act of NEET proteins: Iron, ROS, calcium and metabolism

Nechushtai

Karmi

Zuo

et al. 2020

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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NEET proteins belong to a highly conserved group of [2Fe-2S] proteins found across all kingdoms of life. Due to their unique 2Fe-2S cluster structure, they play a key role in the regulation of many different redox and oxidation processes. In eukaryotes, NEET proteins are localized to the mitochondria, ER and the membranes connecting these organelles (MAM), and are involved in the control of multiple processes, ranging from autophagy and apoptosis to ferroptosis, oxidative stress, cell proliferation, redox control and iron and iron-sulfur homeostasis. Through their different functions and interactions with key proteins such as VDAC and Bcl-2, NEET proteins coordinate different mitochondrial, MAM, ER and cytosolic processes and functions and regulate major signaling molecules such as calcium and reactive oxygen species. Owing to their central role in cells, NEET proteins are associated with numerous human maladies including cancer, metabolic diseases, diabetes, obesity, and neurodegenerative diseases. In recent years, a new and exciting role for NEET proteins was uncovered, i.e., the regulation of mitochondrial dynamics and morphology. This new role places NEET proteins at the forefront of studies into cancer and different metabolic diseases, both associated with the regulation of mitochondrial dynamics. Here we review recent studies focused on the evolution, biological role, and structure of NEET proteins, as well as discuss different studies conducted on NEET protein function using transgenic organisms. We further discuss the different strategies used in the development of drugs that target NEET proteins, and link these with the different roles of NEET proteins in cells.

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“…Wolfram Syndrome Type 2 (WFS-T2) is a rare genetic disease found in several different populations worldwide [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Its early onset is characterized by severe insulin deficiency leading to juvenile onset of diabetes mellitus, progressive appearance of gastro-intestinal (GI) ulcers, abnormal platelet aggregation, sensorineural hearing loss, optical nerve atrophy, and psychosis [ 1 , 8 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

A Combined Drug Treatment That Reduces Mitochondrial Iron and Reactive Oxygen Levels Recovers Insulin Secretion in NAF-1-Deficient Pancreatic Cells

et al. 2021

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Decreased insulin secretion, associated with pancreatic β-cell failure, plays a critical role in many human diseases including diabetes, obesity, and cancer. While numerous studies linked β-cell failure with enhanced levels of reactive oxygen species (ROS), the development of diabetes associated with hereditary conditions that result in iron overload, e.g., hemochromatosis, Friedreich's ataxia, and Wolfram syndrome type 2 (WFS-T2; a mutation in CISD2, encoding the [2Fe-2S] protein NAF-1), underscores an additional link between iron metabolism and β-cell failure. Here, using NAF-1-repressed INS-1E pancreatic cells, we observed that NAF-1 repression inhibited insulin secretion, as well as impaired mitochondrial and ER structure and function. Importantly, we found that a combined treatment with the cell permeant iron chelator deferiprone and the glutathione precursor N-acetyl cysteine promoted the structural repair of mitochondria and ER, decreased mitochondrial labile iron and ROS levels, and restored glucose-stimulated insulin secretion. Additionally, treatment with the ferroptosis inhibitor ferrostatin-1 decreased cellular ROS formation and improved cellular growth of NAF-1 repressed pancreatic cells. Our findings reveal that suppressed expression of NAF-1 is associated with the development of ferroptosis-like features in pancreatic cells, and that reducing the levels of mitochondrial iron and ROS levels could be used as a therapeutic avenue for WFS-T2 patients.

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Previously unreported abnormalities in Wolfram Syndrome Type 2

Cited by 8 publications

References 13 publications

Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum

Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum

The balancing act of NEET proteins: Iron, ROS, calcium and metabolism

A Combined Drug Treatment That Reduces Mitochondrial Iron and Reactive Oxygen Levels Recovers Insulin Secretion in NAF-1-Deficient Pancreatic Cells

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