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Human Genetic Disorders Resulting in Systemic Selenoprotein Deficiency

Selenium, a trace element fundamental to human health, is incorporated as the amino acid selenocysteine (Sec) into more than 25 proteins, referred to as selenoproteins. Human mutations in SECISBP2, SEPSECS and TRU-TCA1-1, three genes essential in the selenocysteine incorporation pathway, affect the...

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Autores principales: Schoenmakers, Erik, Chatterjee, Krishna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658020/
https://www.ncbi.nlm.nih.gov/pubmed/34884733
http://dx.doi.org/10.3390/ijms222312927
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author Schoenmakers, Erik
Chatterjee, Krishna
author_facet Schoenmakers, Erik
Chatterjee, Krishna
author_sort Schoenmakers, Erik
collection PubMed
description Selenium, a trace element fundamental to human health, is incorporated as the amino acid selenocysteine (Sec) into more than 25 proteins, referred to as selenoproteins. Human mutations in SECISBP2, SEPSECS and TRU-TCA1-1, three genes essential in the selenocysteine incorporation pathway, affect the expression of most if not all selenoproteins. Systemic selenoprotein deficiency results in a complex, multifactorial disorder, reflecting loss of selenoprotein function in specific tissues and/or long-term impaired selenoenzyme-mediated defence against oxidative and endoplasmic reticulum stress. SEPSECS mutations are associated with a predominantly neurological phenotype with progressive cerebello-cerebral atrophy. Selenoprotein deficiency due to SECISBP2 and TRU-TCA1-1 defects are characterized by abnormal circulating thyroid hormones due to lack of Sec-containing deiodinases, low serum selenium levels (low SELENOP, GPX3), with additional features (myopathy due to low SELENON; photosensitivity, hearing loss, increased adipose mass and function due to reduced antioxidant and endoplasmic reticulum stress defence) in SECISBP2 cases. Antioxidant therapy ameliorates oxidative damage in cells and tissues of patients, but its longer term benefits remain undefined. Ongoing surveillance of patients enables ascertainment of additional phenotypes which may provide further insights into the role of selenoproteins in human biological processes.
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spelling pubmed-86580202021-12-10 Human Genetic Disorders Resulting in Systemic Selenoprotein Deficiency Schoenmakers, Erik Chatterjee, Krishna Int J Mol Sci Review Selenium, a trace element fundamental to human health, is incorporated as the amino acid selenocysteine (Sec) into more than 25 proteins, referred to as selenoproteins. Human mutations in SECISBP2, SEPSECS and TRU-TCA1-1, three genes essential in the selenocysteine incorporation pathway, affect the expression of most if not all selenoproteins. Systemic selenoprotein deficiency results in a complex, multifactorial disorder, reflecting loss of selenoprotein function in specific tissues and/or long-term impaired selenoenzyme-mediated defence against oxidative and endoplasmic reticulum stress. SEPSECS mutations are associated with a predominantly neurological phenotype with progressive cerebello-cerebral atrophy. Selenoprotein deficiency due to SECISBP2 and TRU-TCA1-1 defects are characterized by abnormal circulating thyroid hormones due to lack of Sec-containing deiodinases, low serum selenium levels (low SELENOP, GPX3), with additional features (myopathy due to low SELENON; photosensitivity, hearing loss, increased adipose mass and function due to reduced antioxidant and endoplasmic reticulum stress defence) in SECISBP2 cases. Antioxidant therapy ameliorates oxidative damage in cells and tissues of patients, but its longer term benefits remain undefined. Ongoing surveillance of patients enables ascertainment of additional phenotypes which may provide further insights into the role of selenoproteins in human biological processes. MDPI 2021-11-29 /pmc/articles/PMC8658020/ /pubmed/34884733 http://dx.doi.org/10.3390/ijms222312927 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Schoenmakers, Erik
Chatterjee, Krishna
Human Genetic Disorders Resulting in Systemic Selenoprotein Deficiency
title Human Genetic Disorders Resulting in Systemic Selenoprotein Deficiency
title_full Human Genetic Disorders Resulting in Systemic Selenoprotein Deficiency
title_fullStr Human Genetic Disorders Resulting in Systemic Selenoprotein Deficiency
title_full_unstemmed Human Genetic Disorders Resulting in Systemic Selenoprotein Deficiency
title_short Human Genetic Disorders Resulting in Systemic Selenoprotein Deficiency
title_sort human genetic disorders resulting in systemic selenoprotein deficiency
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658020/
https://www.ncbi.nlm.nih.gov/pubmed/34884733
http://dx.doi.org/10.3390/ijms222312927
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