A novel heterozygous mutation of the <i>WFS1</i>
 gene leading to constitutive endoplasmic reticulum stress is the cause of Wolfram syndrome

¹

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²

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³

et al. 2022

Abstract

Smart CitationsHow this paper cites the one you are viewing

“…Regarding the protein expression in the inner ear, studies reported that the expression of wolframin protein was observed in different cell types of mice and adult marmoset, including the organ of Corti, spiral ganglion neurons, and supporting cells of the cochlea [ 38 , 39 ]. Morikawa et al showed that both wild-type and mutant WFS1 (i.e., p.N325_I328del, p.Q194X, and p.L543R) were expressed in the ER of HEK-293 cells, which was consistent with our fluorescence results [ 40 ]. To observe the localization of variant wolframin protein in mouse cochlear hair cells, we performed immunofluorescence staining on HEI-OC1 cells and found that the results of HEI-OC1 cells were consistent with those of the HEK-293 T cells.…”

Section: Discussion

supporting

confidence: 92%

“…To observe the localization of variant wolframin protein in mouse cochlear hair cells, we performed immunofluorescence staining on HEI-OC1 cells and found that the results of HEI-OC1 cells were consistent with those of the HEK-293 T cells. Notably, the variants described by Morikawa et al caused WS and resulted in significantly lower levels of variant protein expression in HEK-293 T cells than in WT [40], whereas the variant found in this study did not induce significant changes in wolframin protein levels in cells (Supplementary Figure 1). In addition, the WFS1 variants (i.e., p.N325_ I328del, p.Q194X, and p.L543R) induced constitutive ER stress and cell apoptosis in HEK-293 T cells [40].…”

Section: Discussion

contrasting

confidence: 50%

“…Notably, the variants described by Morikawa et al caused WS and resulted in significantly lower levels of variant protein expression in HEK-293 T cells than in WT [40], whereas the variant found in this study did not induce significant changes in wolframin protein levels in cells (Supplementary Figure 1). In addition, the WFS1 variants (i.e., p.N325_ I328del, p.Q194X, and p.L543R) induced constitutive ER stress and cell apoptosis in HEK-293 T cells [40]. However, the mechanism of LFSNHL caused by WFS1 variants is still unclear.…”

Section: Discussion

contrasting

confidence: 50%

See 2 more Smart Citations

A Novel Missense WFS1 Variant: Expanding the Mutational Spectrum Associated with Nonsyndromic Low‐Frequency Sensorineural Hearing Loss

¹

,

²

,

³

et al. 2022

Abstract

Smart CitationsHow this paper cites the one you are viewing

“…Regarding the protein expression in the inner ear, studies reported that the expression of wolframin protein was observed in different cell types of mice and adult marmoset, including the organ of Corti, spiral ganglion neurons, and supporting cells of the cochlea [ 38 , 39 ]. Morikawa et al showed that both wild-type and mutant WFS1 (i.e., p.N325_I328del, p.Q194X, and p.L543R) were expressed in the ER of HEK-293 cells, which was consistent with our fluorescence results [ 40 ]. To observe the localization of variant wolframin protein in mouse cochlear hair cells, we performed immunofluorescence staining on HEI-OC1 cells and found that the results of HEI-OC1 cells were consistent with those of the HEK-293 T cells.…”

Section: Discussion

supporting

confidence: 92%

“…To observe the localization of variant wolframin protein in mouse cochlear hair cells, we performed immunofluorescence staining on HEI-OC1 cells and found that the results of HEI-OC1 cells were consistent with those of the HEK-293 T cells. Notably, the variants described by Morikawa et al caused WS and resulted in significantly lower levels of variant protein expression in HEK-293 T cells than in WT [40], whereas the variant found in this study did not induce significant changes in wolframin protein levels in cells (Supplementary Figure 1). In addition, the WFS1 variants (i.e., p.N325_ I328del, p.Q194X, and p.L543R) induced constitutive ER stress and cell apoptosis in HEK-293 T cells [40].…”

Section: Discussion

contrasting

confidence: 50%

“…Notably, the variants described by Morikawa et al caused WS and resulted in significantly lower levels of variant protein expression in HEK-293 T cells than in WT [40], whereas the variant found in this study did not induce significant changes in wolframin protein levels in cells (Supplementary Figure 1). In addition, the WFS1 variants (i.e., p.N325_ I328del, p.Q194X, and p.L543R) induced constitutive ER stress and cell apoptosis in HEK-293 T cells [40]. However, the mechanism of LFSNHL caused by WFS1 variants is still unclear.…”

Section: Discussion

contrasting

confidence: 50%

See 1 more Smart Citation

Wolfram syndrome: MAMs’ connection?

Delprat

¹

,

Maurice

²

,

Delettre

³

2018

Cell Death Dis

Abstract

Smart CitationsHow this paper cites the one you are viewing

“…Since SERCA2b is expressed in MAMs and is a well-known effector of ER Ca 2+ uptake 150 , Wfs1 may be a novel MAM physiological effector essential for Ca 2+ homeostasis. In contrast, Morikawa et al 151 described a reduced mRNA level of SERCA2b in HEK-293 cells transfected with mutant WFS1 cDNA compared to HEK-293 cells transfected with wild-type WFS1 cDNA. This elevation of [Ca 2+ ] cyto is associated with an increase of the mRNA level of CCAAT-enhancer-binding protein homologous protein, leading to ER stress-induced cell apoptosis 152 .…”

Section: Is Mams' Dysfunction Playing a Role In Ws1 Pathology?

mentioning

confidence: 84%

ISR inhibition reverses pancreatic β-cell failure in Wolfram syndrome models

Chen

¹

,

Su

²

,

³

et al. 2024

Cell Death Differ

Abstract

Smart CitationsHow this paper cites the one you are viewing

“…The impairment of pancreatic β-cell function and subsequent β-cell death are manifested as a result of WFS1 loss-of-function [8,12,13,28,29]. Previous studies illustrated the role of WFS1 associated with ER stress and UPR [8,15,16,30], and WFS1 preserves β cell function by promoting insulin synthesis and mitigating ER stress [29]. However, deeper mechanism of pancreatic β-cell failure with WFS1 deficiency in WS diabetes remains unclear.…”

Section: Results

mentioning

confidence: 99%

A Novel Missense WFS1 Variant: Expanding the Mutational Spectrum Associated with Nonsyndromic Low‐Frequency Sensorineural Hearing Loss

¹

,

²

,

³

et al. 2022

Abstract

Smart CitationsHow this paper cites the one you are viewing

“…Regarding the protein expression in the inner ear, studies reported that the expression of wolframin protein was observed in different cell types of mice and adult marmoset, including the organ of Corti, spiral ganglion neurons, and supporting cells of the cochlea [ 38 , 39 ]. Morikawa et al showed that both wild-type and mutant WFS1 (i.e., p.N325_I328del, p.Q194X, and p.L543R) were expressed in the ER of HEK-293 cells, which was consistent with our fluorescence results [ 40 ]. To observe the localization of variant wolframin protein in mouse cochlear hair cells, we performed immunofluorescence staining on HEI-OC1 cells and found that the results of HEI-OC1 cells were consistent with those of the HEK-293 T cells.…”

Section: Discussion

supporting

confidence: 92%

“…To observe the localization of variant wolframin protein in mouse cochlear hair cells, we performed immunofluorescence staining on HEI-OC1 cells and found that the results of HEI-OC1 cells were consistent with those of the HEK-293 T cells. Notably, the variants described by Morikawa et al caused WS and resulted in significantly lower levels of variant protein expression in HEK-293 T cells than in WT [40], whereas the variant found in this study did not induce significant changes in wolframin protein levels in cells (Supplementary Figure 1). In addition, the WFS1 variants (i.e., p.N325_ I328del, p.Q194X, and p.L543R) induced constitutive ER stress and cell apoptosis in HEK-293 T cells [40].…”

Section: Discussion

contrasting

confidence: 50%

“…Notably, the variants described by Morikawa et al caused WS and resulted in significantly lower levels of variant protein expression in HEK-293 T cells than in WT [40], whereas the variant found in this study did not induce significant changes in wolframin protein levels in cells (Supplementary Figure 1). In addition, the WFS1 variants (i.e., p.N325_ I328del, p.Q194X, and p.L543R) induced constitutive ER stress and cell apoptosis in HEK-293 T cells [40]. However, the mechanism of LFSNHL caused by WFS1 variants is still unclear.…”

Section: Discussion

contrasting

confidence: 50%

See 1 more Smart Citation

Wolfram syndrome: MAMs’ connection?

Delprat

¹

,

Maurice

²

,

Delettre

³

2018

Cell Death Dis

Abstract

Smart CitationsHow this paper cites the one you are viewing

“…Since SERCA2b is expressed in MAMs and is a well-known effector of ER Ca 2+ uptake 150 , Wfs1 may be a novel MAM physiological effector essential for Ca 2+ homeostasis. In contrast, Morikawa et al 151 described a reduced mRNA level of SERCA2b in HEK-293 cells transfected with mutant WFS1 cDNA compared to HEK-293 cells transfected with wild-type WFS1 cDNA. This elevation of [Ca 2+ ] cyto is associated with an increase of the mRNA level of CCAAT-enhancer-binding protein homologous protein, leading to ER stress-induced cell apoptosis 152 .…”

Section: Is Mams' Dysfunction Playing a Role In Ws1 Pathology?

mentioning

confidence: 84%

ISR inhibition reverses pancreatic β-cell failure in Wolfram syndrome models

Chen

¹

,

Su

²

,

³

et al. 2024

Cell Death Differ

Abstract

Smart CitationsHow this paper cites the one you are viewing

“…The impairment of pancreatic β-cell function and subsequent β-cell death are manifested as a result of WFS1 loss-of-function [8,12,13,28,29]. Previous studies illustrated the role of WFS1 associated with ER stress and UPR [8,15,16,30], and WFS1 preserves β cell function by promoting insulin synthesis and mitigating ER stress [29]. However, deeper mechanism of pancreatic β-cell failure with WFS1 deficiency in WS diabetes remains unclear.…”

Section: Results

mentioning

confidence: 99%

A Novel Missense WFS1 Variant: Expanding the Mutational Spectrum Associated with Nonsyndromic Low‐Frequency Sensorineural Hearing Loss

¹

,

²

,

³

et al. 2022

Abstract

Smart CitationsHow this paper cites the one you are viewing

“…Regarding the protein expression in the inner ear, studies reported that the expression of wolframin protein was observed in different cell types of mice and adult marmoset, including the organ of Corti, spiral ganglion neurons, and supporting cells of the cochlea [ 38 , 39 ]. Morikawa et al showed that both wild-type and mutant WFS1 (i.e., p.N325_I328del, p.Q194X, and p.L543R) were expressed in the ER of HEK-293 cells, which was consistent with our fluorescence results [ 40 ]. To observe the localization of variant wolframin protein in mouse cochlear hair cells, we performed immunofluorescence staining on HEI-OC1 cells and found that the results of HEI-OC1 cells were consistent with those of the HEK-293 T cells.…”

Section: Discussion

supporting

confidence: 92%

“…To observe the localization of variant wolframin protein in mouse cochlear hair cells, we performed immunofluorescence staining on HEI-OC1 cells and found that the results of HEI-OC1 cells were consistent with those of the HEK-293 T cells. Notably, the variants described by Morikawa et al caused WS and resulted in significantly lower levels of variant protein expression in HEK-293 T cells than in WT [40], whereas the variant found in this study did not induce significant changes in wolframin protein levels in cells (Supplementary Figure 1). In addition, the WFS1 variants (i.e., p.N325_ I328del, p.Q194X, and p.L543R) induced constitutive ER stress and cell apoptosis in HEK-293 T cells [40].…”

Section: Discussion

contrasting

confidence: 50%

“…Notably, the variants described by Morikawa et al caused WS and resulted in significantly lower levels of variant protein expression in HEK-293 T cells than in WT [40], whereas the variant found in this study did not induce significant changes in wolframin protein levels in cells (Supplementary Figure 1). In addition, the WFS1 variants (i.e., p.N325_ I328del, p.Q194X, and p.L543R) induced constitutive ER stress and cell apoptosis in HEK-293 T cells [40]. However, the mechanism of LFSNHL caused by WFS1 variants is still unclear.…”

Section: Discussion

contrasting

confidence: 50%

See 1 more Smart Citation

Wolfram syndrome: MAMs’ connection?

Delprat

¹

,

Maurice

²

,

Delettre

³

2018

Cell Death Dis

Abstract

Smart CitationsHow this paper cites the one you are viewing

“…Since SERCA2b is expressed in MAMs and is a well-known effector of ER Ca 2+ uptake 150 , Wfs1 may be a novel MAM physiological effector essential for Ca 2+ homeostasis. In contrast, Morikawa et al 151 described a reduced mRNA level of SERCA2b in HEK-293 cells transfected with mutant WFS1 cDNA compared to HEK-293 cells transfected with wild-type WFS1 cDNA. This elevation of [Ca 2+ ] cyto is associated with an increase of the mRNA level of CCAAT-enhancer-binding protein homologous protein, leading to ER stress-induced cell apoptosis 152 .…”

Section: Is Mams' Dysfunction Playing a Role In Ws1 Pathology?

mentioning

confidence: 84%

ISR inhibition reverses pancreatic β-cell failure in Wolfram syndrome models

Chen

¹

,

Su

²

,

³

et al. 2024

Cell Death Differ

Abstract

Smart CitationsHow this paper cites the one you are viewing

“…The impairment of pancreatic β-cell function and subsequent β-cell death are manifested as a result of WFS1 loss-of-function [8,12,13,28,29]. Previous studies illustrated the role of WFS1 associated with ER stress and UPR [8,15,16,30], and WFS1 preserves β cell function by promoting insulin synthesis and mitigating ER stress [29]. However, deeper mechanism of pancreatic β-cell failure with WFS1 deficiency in WS diabetes remains unclear.…”

Section: Results

mentioning

confidence: 99%