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 <i>SECISBP2</i>, <i>SEPSECS</i> and <i>TRU-TCA1-1</i>, three genes essential...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/23/12927 |
| _version_ | 1797507690387210240 |
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| author | Erik Schoenmakers Krishna Chatterjee |
| author_facet | Erik Schoenmakers Krishna Chatterjee |
| author_sort | Erik Schoenmakers |
| collection | DOAJ |
| 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 <i>SECISBP2</i>, <i>SEPSECS</i> and <i>TRU-TCA1-1</i>, 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. <i>SEPSECS</i> mutations are associated with a predominantly neurological phenotype with progressive cerebello-cerebral atrophy. Selenoprotein deficiency due to <i>SECISBP2</i> and <i>TRU-TCA1-1</i> 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 <i>SECISBP2</i> 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. |
| first_indexed | 2024-03-10T04:52:01Z |
| format | Article |
| id | doaj.art-2a51e44e77244989ae133ba26ad000c5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:52:01Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2a51e44e77244989ae133ba26ad000c52023-11-23T02:30:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231292710.3390/ijms222312927Human Genetic Disorders Resulting in Systemic Selenoprotein DeficiencyErik Schoenmakers0Krishna Chatterjee1Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UKMetabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UKSelenium, 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 <i>SECISBP2</i>, <i>SEPSECS</i> and <i>TRU-TCA1-1</i>, 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. <i>SEPSECS</i> mutations are associated with a predominantly neurological phenotype with progressive cerebello-cerebral atrophy. Selenoprotein deficiency due to <i>SECISBP2</i> and <i>TRU-TCA1-1</i> 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 <i>SECISBP2</i> 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.https://www.mdpi.com/1422-0067/22/23/12927selenoprotein deficiencySECISBP2Sec-tRNA<sup>[Ser]Sec</sup>SEPSECSselenium |
| spellingShingle | Erik Schoenmakers Krishna Chatterjee Human Genetic Disorders Resulting in Systemic Selenoprotein Deficiency International Journal of Molecular Sciences selenoprotein deficiency SECISBP2 Sec-tRNA<sup>[Ser]Sec</sup> SEPSECS selenium |
| 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 | selenoprotein deficiency SECISBP2 Sec-tRNA<sup>[Ser]Sec</sup> SEPSECS selenium |
| url | https://www.mdpi.com/1422-0067/22/23/12927 |
| work_keys_str_mv | AT erikschoenmakers humangeneticdisordersresultinginsystemicselenoproteindeficiency AT krishnachatterjee humangeneticdisordersresultinginsystemicselenoproteindeficiency |