Multiplex PCR-based Sequencing of ATP7B Gene in Wilson's Disease – A Preliminary Study

Aaron, Rekha; Chapla, Aaron; Danda, Sumita; Zachariah, Uday; Eapen, C E; Goel, Ashish

doi:10.1016/j.jceh.2021.08.001

Cited by 3 publications

(1 citation statement)

References 11 publications

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“…The correlation between genotype and phenotype for these variants is controversial. While some papers document severe neurological impairment and K–F rings in patients during the first or early second decade of life, others report hepatic presentations [ [24] , [25] , [26] , [27] , [28] ]. It is worth mentioning that most studies have reported a lack of correlation between ATP7B gene variants and the phenotype.…”

Section: Genotype-phenotype Correlationmentioning

confidence: 99%

The mutation spectrum and ethnic distribution of Wilson disease, a review

Beyzaei,

Mehrzadeh,

Hashemi

et al. 2024

Molecular Genetics and Metabolism Reports

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Section: Genotype-phenotype Correlationmentioning

confidence: 99%

The mutation spectrum and ethnic distribution of Wilson disease, a review

Beyzaei,

Mehrzadeh,

Hashemi

et al. 2024

Molecular Genetics and Metabolism Reports

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FoxO1 silencing in Atp7b^−/− neural stem cells attenuates high copper‐induced apoptosis via regulation of autophagy

Zhang,

Wang,

Tang

et al. 2024

Journal of Neurochemistry

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Wilson disease (WD) is a severely autosomal genetic disorder triggered by dysregulated copper metabolism. Autophagy and apoptosis share common modulators that process cellular death. Emerging evidences suggest that Forkhead Box O1 over‐expression (FoxO1‐OE) aggravates abnormal autophagy and apoptosis to induce neuronal injury. However, the underlying mechanisms remain undetermined. Herein, the aim of this study was to investigate how regulating FoxO1 affects cellular autophagy and apoptosis to attenuate neuronal injury in a well‐established WD cell model, the high concentration copper sulfate (CuSO4, HC)‐triggered Atp7b−/− (Knockout, KO) neural stem cell (NSC) lines. The FoxO1‐OE plasmid, or siRNA‐FoxO1 (siFoxO1) plasmid, or empty vector plasmid was stably transfected with recombinant lentiviral vectors into HC‐induced Atp7b−/− NSCs. Toxic effects of excess deposited copper on wild‐type (WT), Atp7b−/− WD mouse hippocampal NSCs were tested by Cell Counting Kit‐8 (CCK‐8). Subsequently, the FoxO1 expression was evaluated by immunofluorescence (IF) assay, western blot (WB) and quantitative real‐time polymerase chain reaction (qRT‐PCR) analysis. Meanwhile, the cell autophagy and apoptosis were evaluated by flow cytometry (FC), TUNEL staining, 2,7‐dichlorofluorescein diacetate (DCFH‐DA), JC‐1, WB, and qRT‐PCR. The current study demonstrated a strong rise in FoxO1 levels in HC‐treated Atp7b−/− NSCs, accompanied with dysregulated autophagy and hyperactive apoptosis. Also, it was observed that cell viability was significantly decreased with the over‐expressed FoxO1 in HC‐treated Atp7b−/− WD model. As intended, silencing FoxO1 effectively inhibited abnormal autophagy in HC‐treated Atp7b−/− NSCs, as depicted by a decline in LC3II/I, Beclin‐1, ATG3, ATG7, ATG13, and ATG16, whereas simultaneously increasing P62. In addition, silencing FoxO1 suppressed apoptosis via diminishing oxidative stress (OS), and mitochondrial dysfunction in HC‐induced Atp7b−/− NSCs. Collectively, these results clearly demonstrate the silencing FoxO1 has the neuroprotective role of suppressing aberrant cellular autophagy and apoptosis, which efficiently attenuates neuronal injury in WD.image

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Rhodanine Stain Improves Utility of Leipzig Score to Diagnose Hepatic Wilson’s Disease in Noncholestatic Patients with Fibrosis

Vijayalekshmi,

Kodiatte,

Amirtharaj

et al. 2023

Gastroenterology, Hepatology and Endoscopy Practice

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Introduction: Cholestasis may increase the difficulty of diagnosing Wilson’s disease (WD). We aimed to compare Leipzig score including hepatic parenchymal copper concentration or rhodanine stain, to diagnose hepatic WD, in noncholestatic patients with fibrosis. Materials and Methods: We defined cholestasis by biochemical and/or histological criteria. Of noncholestatic patients who had liver fibrosis and liver copper estimation, those with isolated hepatic WD comprised WD study group and those with liver disease other than WD, with either low serum ceruloplasmin, high urinary copper, or Kayser–Fleischer ring, were controls. WD diagnosis by Leipzig score was labeled highly likely, probable, or unlikely. Results: Twenty WD study group patients (12 males; 21 [6–52] years; median [range]) and 18 controls (13 males; 32 [10–69] years, all had high urinary copper) were recruited. Rhodanine stain was positive in 60% WD patients and in 33% of controls. With rhodanine stain, Leipzig score had sensitivity of 100% (95% confidence interval: 83.2%–100%), specificity of 66.7% (41%–86.7%), and positive likelihood ratio of 3 (1.56–5.77) to diagnose probable/highly likely WD. In contrast, on adding hepatic parenchymal copper concentration, Leipzig score had sensitivity of 100% (83.2%–100%), but specificity was 38.9% (17.3%–64.2%). In controls, Leipzig score (including rhodanine stain) of ≤ 2 ruled out WD. Conclusion: On excluding cholestatic patients, rhodanine stain performs better than hepatic parenchymal copper concentration to diagnose hepatic WD using Leipzig score in patients with fibrosis. Widespread availability is an added advantage of rhodanine stain.

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Multiplex PCR-based Sequencing of ATP7B Gene in Wilson's Disease – A Preliminary Study

Cited by 3 publications

References 11 publications

The mutation spectrum and ethnic distribution of Wilson disease, a review

The mutation spectrum and ethnic distribution of Wilson disease, a review

FoxO1 silencing in Atp7b^−/− neural stem cells attenuates high copper‐induced apoptosis via regulation of autophagy

Rhodanine Stain Improves Utility of Leipzig Score to Diagnose Hepatic Wilson’s Disease in Noncholestatic Patients with Fibrosis

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Multiplex PCR-based Sequencing of ATP7B Gene in Wilson's Disease – A Preliminary Study

Cited by 3 publications

References 11 publications

The mutation spectrum and ethnic distribution of Wilson disease, a review

The mutation spectrum and ethnic distribution of Wilson disease, a review

FoxO1 silencing in Atp7b−/− neural stem cells attenuates high copper‐induced apoptosis via regulation of autophagy

Rhodanine Stain Improves Utility of Leipzig Score to Diagnose Hepatic Wilson’s Disease in Noncholestatic Patients with Fibrosis

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FoxO1 silencing in Atp7b^−/− neural stem cells attenuates high copper‐induced apoptosis via regulation of autophagy