@article{cb1632190f19470bb79139b43e23a92d,
title = "Mutations in SECISBP2 result in abnormal thyroid hormone metabolism",
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.",
author = "Dumitrescu, {Alexandra M.} and Liao, {Xiao Hui} and Abdullah, {Mohamed S.Y.} and Joaquin Lado-Abeal and Majed, {Fathia Abdul} and Moeller, {Lars C.} and Gerard Boran and Lutz Schomburg and Weiss, {Roy E.} and Samuel Refetoff",
note = "Funding Information: We thank N.H. Scherberg and his laboratory staff for doing the tests of thyroid function in sera; all members of the families for their willingness to participate in this study; I. Abo Alnoor and A. Abomelha for their help and support; H. Hoey and M. Adress for referral of the proband of family B; M.-S. McPeek and U. Schweizer for advice; A. Hernandez and D. St. Germain for their efforts to measure DIO3 enzymatic activity in fibroblasts; J. K{\"o}hrle for his advice and help with selenoprotein analysis; K.J. Millen, G.I. Bell and D.F. Steiner for critical reading of the manuscript; F.E. Wondisford for contributing to Figure 1; and V.A. Galton for sharing with us unpublished data on the mice with combined Dio1 and Dio2 targeted disruption and for allowing us to mention these data as personal communication. This work was supported in part by grants from the US National Institutes of Health and from the Deutsche Forschungsgemeinschaft. A.M.D. is a Howard Hughes Medical Institute Predoctoral Fellow. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.",
year = "2005",
month = nov,
doi = "10.1038/ng1654",
language = "English (US)",
volume = "37",
pages = "1247--1252",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "11",
}