Mutations in SECISBP2 result in abnormal thyroid hormone metabolism

Alexandra M. Dumitrescu, Xiao Hui Liao, Mohamed S Y Abdullah, Joaquin Lado-Abeal, Fathia Abdul Majed, Lars C. Moeller, Gerard Boran, Lutz Schomburg, Roy E Weiss, Samuel Refetoff

Research output: Contribution to journalArticle

246 Citations (Scopus)

Abstract

Incorporation of selenocysteine (Sec), through recoding of the UGA stop codon, creates a unique class of proteins. Mice lacking tRNASec die in utero, but the in vivo role of other components involved in selenoprotein synthesis is unknown, and Sec incorporation defects have not been described in humans. Deiodinases (DIOs) are selenoproteins involved in thyroid hormone metabolism. We identified three of seven siblings with clinical evidence of abnormal thyroid hormone metabolism. Their fibroblasts showed decreased DIO2 enzymatic activity not linked to the DIO2 locus. Systematic linkage analysis of genes involved in DIO2 synthesis and degradation led to the identification of an inherited Sec incorporation defect, caused by a homozygous missense mutation in SECISBP2 (also called SBP2). An unrelated child with a similar phenotype was compound heterozygous with respect to mutations in SECISBP2. Because SBP2 is epistatic to selenoprotein synthesis, these defects had a generalized effect on selenoproteins. Incomplete loss of SBP2 function probably causes the mild phenotype.

Original languageEnglish (US)
Pages (from-to)1247-1252
Number of pages6
JournalNature Genetics
Volume37
Issue number11
DOIs
StatePublished - Nov 2005
Externally publishedYes

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Selenoproteins
Selenocysteine
Mutation
Phenotype
Iodide Peroxidase
Terminator Codon
Missense Mutation
Thyroid Hormones
Siblings
Fibroblasts
Abnormal Thyroid Hormone Metabolism
Genes
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Dumitrescu, A. M., Liao, X. H., Abdullah, M. S. Y., Lado-Abeal, J., Majed, F. A., Moeller, L. C., ... Refetoff, S. (2005). Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. Nature Genetics, 37(11), 1247-1252. https://doi.org/10.1038/ng1654

Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. / Dumitrescu, Alexandra M.; Liao, Xiao Hui; Abdullah, Mohamed S Y; Lado-Abeal, Joaquin; Majed, Fathia Abdul; Moeller, Lars C.; Boran, Gerard; Schomburg, Lutz; Weiss, Roy E; Refetoff, Samuel.

In: Nature Genetics, Vol. 37, No. 11, 11.2005, p. 1247-1252.

Research output: Contribution to journalArticle

Dumitrescu, AM, Liao, XH, Abdullah, MSY, Lado-Abeal, J, Majed, FA, Moeller, LC, Boran, G, Schomburg, L, Weiss, RE & Refetoff, S 2005, 'Mutations in SECISBP2 result in abnormal thyroid hormone metabolism', Nature Genetics, vol. 37, no. 11, pp. 1247-1252. https://doi.org/10.1038/ng1654
Dumitrescu AM, Liao XH, Abdullah MSY, Lado-Abeal J, Majed FA, Moeller LC et al. Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. Nature Genetics. 2005 Nov;37(11):1247-1252. https://doi.org/10.1038/ng1654
Dumitrescu, Alexandra M. ; Liao, Xiao Hui ; Abdullah, Mohamed S Y ; Lado-Abeal, Joaquin ; Majed, Fathia Abdul ; Moeller, Lars C. ; Boran, Gerard ; Schomburg, Lutz ; Weiss, Roy E ; Refetoff, Samuel. / Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. In: Nature Genetics. 2005 ; Vol. 37, No. 11. pp. 1247-1252.
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