Clinical and Molecular Characterization of a Novel Selenocysteine Insertion Sequence-Binding Protein 2 (SBP2) Gene Mutation (R128X)

Cosmo, Caterina Di; McLellan, Neil; Liao, Xiao-Hui; Khanna, Kum Kum; Weiss, Roy E.; Papp, Laura Vanda; Refetoff, Samuel

doi:10.1210/jc.2009-0686

Cited by 99 publications

(99 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, increased levels of SBP2 differentially influence insertion of Sec into individual selenoproteins, suggesting that efficiency of this process is likely determined by the structure of SECIS elements and their different affinity for SBP2 (231,322). These findings are further supported by a recent discovery of mutations in the SBP2 gene in patients with hypothyroidism caused by defects in synthesis of type 2 deiodinase (DI2), a selenoprotein involved in thyroid hormone activation (14, 80,90,306). In one of the affected families, DI2 deficiency was caused by a homozygous missence mutation (R540Q) in the RNA-binding domain of SBP2 (90).…”

Section: B Sbp2mentioning

confidence: 90%

Selenoproteins: Molecular Pathways and Physiological Roles

Labunskyy

Hatfield

Gladyshev³

2014

Physiological Reviews

1,028

835

View full text Add to dashboard Cite

Selenium is an essential micronutrient with important functions in human health and relevance to several pathophysiological conditions. The biological effects of selenium are largely mediated by selenium-containing proteins (selenoproteins) that are present in all three domains of life. Although selenoproteins represent diverse molecular pathways and biological functions, all these proteins contain at least one selenocysteine (Sec), a seleniumcontaining amino acid, and most serve oxidoreductase functions. Sec is cotranslationally inserted into nascent polypeptide chains in response to the UGA codon, whose normal function is to terminate translation. To decode UGA as Sec, organisms evolved the Sec insertion machinery that allows incorporation of this amino acid at specific UGA codons in a process requiring a cis-acting Sec insertion sequence (SECIS) element. Although the basic mechanisms of Sec synthesis and insertion into proteins in both prokaryotes and eukaryotes have been studied in great detail, the identity and functions of many selenoproteins remain largely unknown. In the last decade, there has been significant progress in characterizing selenoproteins and selenoproteomes and understanding their physiological functions. We discuss current knowledge about how these unique proteins perform their functions at the molecular level and highlight new insights into the roles that selenoproteins play in human health.

show abstract

Section: B Sbp2mentioning

confidence: 90%

Selenoproteins: Molecular Pathways and Physiological Roles

Labunskyy

Hatfield

Gladyshev³

2014

Physiological Reviews

1,028

835

View full text Add to dashboard Cite

show abstract

“…Failure of this mechanism can result in miscoding of the UGA codon to be read as a stop codon resulting in an untruncated inactive deiodinase protein. The important role of deiodinases in thyroid economy has been recently emphasized by the discovery of several families with a genetic mutation in SBP2 that is either homozygous or compound heterozygous (114)(115)(116). Patients harboring these mutations present an abnormal thyroid profile characterized by low T3, high T4 and high rT3 concentrations and high normal TSH in serum.…”

Section: Deiodinase Deficiency Due To Inhibition Of Selenoprotein Synmentioning

confidence: 99%

Physiological role and regulation of iodothyronine deiodinases: A 2011 update

Marsili

Zavacki

Harney

et al. 2011

J Endocrinol Invest

View full text Add to dashboard Cite

Thyroxine (T4) is a prohormone secreted by the thyroid. T4 has a long half life in circulation and it is tightly regulated to remain constant in a variety of circumstances. However, the availability of iodothyronine selenodeiodinases allow both the initiation or the cessation of thyroid hormone action and can result in surprisingly acute changes in the intracellular concentration of the active hormone T3, in a tissue-specific and chronologically-determined fashion, in spite of the constant circulating levels of the prohormone. This fine-tuning of thyroid hormone signaling is becoming widely appreciated in the context of situations where the rapid modifications in intracellular T3 concentrations are necessary for developmental changes or tissue repair. Given the increasing availability of genetic models of deiodinase deficiency, new insights into the role of these important enzymes are being recognized. In this review, we have incorporated new information regarding the special role played by these enzymes into our current knowledge of thyroid physiology, emphasizing the clinical significance of these new insights.

show abstract

“…Although a total of 8 families have been identified over the period of 6 years [8,[110][111][112][113] [Dumitrescu, A.M. and Refetoff, S, unpublished data], failure of detection is likely due to the relatively mild clinical symptoms in some subjects. The inheritance is autosomal recessive and males and females are equally affected.…”

Section: Geneticsmentioning

confidence: 99%