Inherited Selenocysteine Transfer RNA Mutation: Clinical and Hormonal Evaluation of 2 Patients

Clinical Thyroidology / Case Report

Geslot A.a· Savagner F.b· Caron P.a

Author affiliations

aDepartment of Endocrinology and metabolic diseases, CHU Larrey, Toulouse, France
bLaboratory of Biochemistry, CHU Purpan, Toulouse, France

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Article / Publication Details

First-Page Preview

Abstract of Clinical Thyroidology / Case Report

Received: November 03, 2020
Accepted: June 29, 2021
Published online: August 26, 2021

Number of Print Pages: 6
Number of Figures: 0
Number of Tables: 4

ISSN: 2235-0640 (Print)
eISSN: 2235-0802 (Online)

For additional information: https://www.karger.com/ETJ

Abstract

Introduction: Iodothyronine deiodinases are selenoproteins with the amino acid selenocysteine (Sec) introduced into the position of a TGA stop codon by a complex machinery involving tRNA[Ser]Sec when a cis-acting Sec-insertion sequence element is present in the 3′ end of the mRNA. Recently, a variant in the TRU-TCA1-1 gene encoding for tRNA[Ser]Sec was reported, which resulted in reduced expression of stress-related selenoproteins. The proband presented with multisystem symptoms, euthyroid hyperthyroxinemia, and selenium deficiency. Here, we describe 2 new members of a family harboring the same tRNA[Ser]Sec variant. Case Presentation: A 13-year-old patient was seen for Hashimoto’s disease with high FT3 (4.6 pg/mL, normal range 2–4.2 pg/mL) and normal FT4 and TSH concentrations. He had no clinical complaints. During a 6-year clinical and hormonal follow-up, the index patient was not treated, FT3 decreased, FT4 increased, and serum TSH stayed in the normal range resulting in a euthyroid hyperthyroxinemia. Reverse T3 concentration was significantly increased at the last visit (19 years and 4 months). At the last evaluation, the total selenium level was low (91 μg/L, normal range 95–125). DNA sequencing identified a germinal homozygous variant (C65G) in the TRU-TCA1-1 gene. During follow-up, no additional clinical symptom was observed in the absence of any treatment. The same germinal tRNA[Ser]Sec variant was identified at heterozygous state in his father, who had normal thyroid function tests except a moderately increased reverse T3 concentration, with increased total selenium (143 μg/L) level. In both patients, the expression of stress-related selenoprotein GPX3 was in the low-normal range (168 and 180 IU/L, respectively, normal range: 150–558 IU/L). We did not find any significant biological abnormalities evocative of other selenoprotein deficiencies. Discussion/Conclusion: We report on 2 members of a family with a variant in the TRU-TCA1-1 gene encoding for tRNA[Ser]Sec. Our study suggests that this tRNA[Ser]Sec variant is not exclusively causative of disruption in selenoprotein synthesis.

© 2021 European Thyroid Association Published by S. Karger AG, Basel

References Arthur JR, Bermano G, Mitchell JH, Hesketh JE. Regulation of selenoprotein gene expression and thyroid hormone metabolism. Biochem Soc Trans. 1996 May;24(2):384–8. Drutel A, Archambeaud F, Caron P. Selenium and the thyroid gland: more good news for clinicians. Clin Endocrinol. 2013 Feb;78(2):155–64. Shetty SP, Copeland PR. Selenocysteine incorporation: a trump card in the game of mRNA decay. Biochimie. 2015 Jul;114:97–101. Labunskyy VM, Hatfield DL, Gladyshev VN. Selenoproteins: molecular pathways and physiological roles. Physiol Rev. 2014 Jul;94(3):739–77. Schoenmakers E, Carlson B, Agostini M, Moran C, Rajanayagam O, Bochukova E, et al. Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis. J Clin Invest. 2016 Mar;126(3):992–6. Schoenmakers E, Agostini M, Mitchell C, Schoenmakers N, Papp L, Rajanayagam O, et al. Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans. J Clin Invest. 2010 Dec;120(12):4220–35. Fradejas-Villar N. Consequences of mutations and inborn errors of selenoprotein biosynthesis and functions. Free Radic Biol Med. 2018 Nov;127:206–14. Di Cosmo C, McLellan N, Liao XH, Khanna KK, Weiss RE, Papp L, et al. Clinical and molecular characterization of a novel selenocysteine insertion sequence-binding protein 2 (SBP2) gene mutation (R128X). J Clin Endocrinol Metab. 2009 Oct;94(10):4003–9. Schomburg L, Dumitrescu AM, Liao XH, Bin-Abbas B, Hoeflich J, Köhrle J, et al. Selenium supplementation fails to correct the selenoprotein synthesis defect in subjects with SBP2 gene mutations. Thyroid. 2009 Mar;19(3):277–81. Kim LK, Matsufuji T, Matsufuji S, Carlson BA, Kim SS, Hatfield DL, et al. Methylation of the ribosyl moiety at position 34 of selenocysteine tRNA[Ser]Sec is governed by both primary and tertiary structure. RNA. 2000 Sep;6(9):1306–15. Kim JY, Carlson BA, Xu XM, Zeng Y, Chen S, Gladyshev VN, et al. Inhibition of selenocysteine tRNA[Ser]Sec aminoacylation provides evidence that aminoacylation is required for regulatory methylation of this tRNA. Biochem Biophys Res Commun. 2011 Jun;409(4):814–9. Hatfield D, Lee BJ, Hampton L, Diamond AM. Selenium induces changes in the selenocysteine tRNA[Ser]Sec population in mammalian cells. Nucleic Acids Res. 1991 Feb;19(4):939–43. Diamond AM, Choi IS, Crain PF, Hashizume T, Pomerantz SC, Cruz R, et al. Dietary selenium affects methylation of the wobble nucleoside in the anticodon of selenocysteine tRNA([Ser]Sec). J Biol Chem. 1993 Jul;268(19):14215–23. Schoenmakers E, Chatterjee K. Identification of genetic disorders causing disruption of selenoprotein biosynthesis. Methods Mol Biol. 2018;1661:325–35. Peskin AV, Winterbourn CC. A microtiter plate assay for superoxide dismutase using a water-soluble tetrazolium salt (WST-1). Clin Chim Acta. 2000 Mar;293(1–2):157–66. Dumitrescu AM, Liao XH, Abdullah MS, Lado-Abeal J, Majed FA, Moeller LC, et al. Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. Nat Genet. 2005 Nov;37(11):1247–52. Germain DL, Hernandez A, Schneider MJ, Galton VA. Insights into the role of deiodinases from studies of genetically modified animals. Thyroid. 2005 Aug;15(8):905–16. Taylor PN, Sayers A, Okosieme O, Das G, Draman MS, Tabasum A, et al. Maturation in serum thyroid function parameters over childhood and puberty: results of a Longitudinal Study. J Clin Endocrinol Metab. 2017 Jul;102(7):2508–15. Marwaha RK, Tandon N, Desai AK, Kanwar R, Sastry A, Narang A, et al. The evolution of thyroid function with puberty. Clin Endocrinol. 2012 Jun;76(6):899–904. Tobe R, Mihara H. Delivery of selenium to selenophosphate synthetase for selenoprotein biosynthesis. Biochim Biophys Acta Gen Subj. 2018 Jun;1862(18):2433–40. Zhu K, Jiang L, Chu Y, Zhang YS. Protective effect of selenium against cisplatin-induced nasopharyngeal cancer in male albino rats. Oncol Lett. 2016 Dec;12(6):5068–74. Woo HA, Yim SH, Shin DH, Kang D, Yu DY, Rhee SG. Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. Cell. 2010 Feb 19;140(4):517–28. Méplan C. Association of single nucleotide polymorphisms in selenoprotein genes with cancer risk. Methods Mol Biol. 2018;1661:313–24. Guo L, Yang W, Huang Q, Qiang J, Hart JR, Wang W, et al. Selenocysteine-specific mass spectrometry reveals tissue-distinct selenoproteomes and candidate selenoproteins. Cell Chem Biol. 2018 Nov;25(11):1380–8.e4. Article / Publication Details

First-Page Preview

Abstract of Clinical Thyroidology / Case Report

Received: November 03, 2020
Accepted: June 29, 2021
Published online: August 26, 2021

Number of Print Pages: 6
Number of Figures: 0
Number of Tables: 4

ISSN: 2235-0640 (Print)
eISSN: 2235-0802 (Online)

For additional information: https://www.karger.com/ETJ

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