p.<scp>P1379S</scp>, a benign variant with reduced <scp>ATP7B</scp> protein level in Wilson Disease

Poskanzer, Sheri A.; Myers, Candace T.; Thies, Jenny; Collins, Christopher; Dayuha, Remwilyn; Duong, Phi; Houwen, Roderick H. J.; Hahn, Si Houn

doi:10.1002/jmd2.12127

Cited by 3 publications

(1 citation statement)

References 24 publications

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“…Evidence of interactions between gene variants that alter their subcellular localisation and trafficking pattern has recently been reported in human populations (Roy et al., 2020). The role of heterozygosity for the ATP7B gene on copper homeostasis requires further investigation (Yi et al., 2020).…”

Section: Assessmentmentioning

confidence: 99%

Re‐evaluation of the existing health‐based guidance values for copper and exposure assessment from all sources

More¹,

Bampidis²,

Benford³

et al. 2023

EFS2

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Copper is an essential micronutrient and also a regulated product used in organic and in conventional farming pest management. Both deficiency and excessive exposure to copper can have adverse health effects. In this Scientific Opinion, the EFSA 2021 harmonised approach for establishing health‐based guidance values (HBGVs) for substances that are regulated products and also nutrients was used to resolve the divergent existing HBGVs for copper. The tightly regulated homeostasis prevents toxicity manifestation in the short term, but the development of chronic copper toxicity is dependent on copper homeostasis and its tissue retention. Evidence from Wilson disease suggests that hepatic retention is indicative of potential future and possibly sudden onset of copper toxicity under conditions of continuous intake. Hence, emphasis was placed on copper retention as an early marker of potential adverse effects. The relationships between (a) chronic copper exposure and its retention in the body, particularly the liver, and (b) hepatic copper concentrations and evidence of toxicity were examined. The Scientific Committee (SC) concludes that no retention of copper is expected to occur with intake of 5 mg/day and established an Acceptable Daily Intake (ADI) of 0.07 mg/kg bw. A refined dietary exposure assessment was performed, assessing contribution from dietary and non‐dietary sources. Background copper levels are a significant source of copper. The contribution of copper from its use as plant protection product (PPP), food and feed additives or fertilisers is negligible. The use of copper in fertilisers or PPPs contributes to copper accumulation in soil. Infant formula and follow‐on formula are important contributors to dietary exposure of copper in infants and toddlers. Contribution from non‐oral sources is negligible. Dietary exposure to total copper does not exceed the HBGV in adolescents, adults, elderly and the very elderly. Neither hepatic copper retention nor adverse effects are expected to occur from the estimated copper exposure in children due to higher nutrient requirements related to growth.

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Section: Assessmentmentioning

confidence: 99%

Re‐evaluation of the existing health‐based guidance values for copper and exposure assessment from all sources

More¹,

Bampidis²,

Benford³

et al. 2023

EFS2

View full text Add to dashboard Cite

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Disorders in the Transport of Copper, Iron, Magnesium, Manganese, Selenium and Zinc

Hasselt¹,

Clayton²,

Houwen³

2022

Inborn Metabolic Diseases

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Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis

Almes

Spraul

Ruiz³

et al. 2022

Diagnostics

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Background: Cholestasis is a frequent and severe condition during childhood. Genetic cholestatic diseases represent up to 25% of pediatric cholestasis. Molecular analysis by targeted-capture next generation sequencing (NGS) has recently emerged as an efficient diagnostic tool. The objective of this study is to evaluate the use of NGS in children with cholestasis. Methods: Children presenting cholestasis were included between 2015 and 2020. Molecular sequencing was performed by targeted capture of a panel of 34 genes involved in cholestasis and jaundice. Patients were classified into three categories: certain diagnosis; suggested diagnosis (when genotype was consistent with phenotype for conditions without any available OMIM or ORPHANET-number); uncertain diagnosis (when clinical and para-clinical findings were not consistent enough with molecular findings). Results: A certain diagnosis was established in 169 patients among the 602 included (28.1%). Molecular studies led to a suggested diagnosis in 40 patients (6.6%) and to an uncertain diagnosis in 21 patients (3.5%). In 372 children (61.7%), no molecular defect was identified. Conclusions: NGS is a useful diagnostic tool in pediatric cholestasis, providing a certain diagnosis in 28.1% of the patients included in this study. In the remaining patients, especially those with variants of uncertain significance, the imputability of the variants requires further investigations.

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p.P1379S, a benign variant with reduced ATP7B protein level in Wilson Disease

Cited by 3 publications

References 24 publications

Re‐evaluation of the existing health‐based guidance values for copper and exposure assessment from all sources

Re‐evaluation of the existing health‐based guidance values for copper and exposure assessment from all sources

Disorders in the Transport of Copper, Iron, Magnesium, Manganese, Selenium and Zinc

Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis

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