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 language | English (US) |
|---|---|
| Pages (from-to) | 1247-1252 |
| Number of pages | 6 |
| Journal | Nature Genetics |
| Volume | 37 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
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 journal › Article
}
TY - JOUR
T1 - Mutations in SECISBP2 result in abnormal thyroid hormone metabolism
AU - Dumitrescu, Alexandra M.
AU - Liao, Xiao Hui
AU - Abdullah, Mohamed S Y
AU - Lado-Abeal, Joaquin
AU - Majed, Fathia Abdul
AU - Moeller, Lars C.
AU - Boran, Gerard
AU - Schomburg, Lutz
AU - Weiss, Roy E
AU - Refetoff, Samuel
PY - 2005/11
Y1 - 2005/11
N2 - 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.
AB - 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.
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U2 - 10.1038/ng1654
DO - 10.1038/ng1654
M3 - Article
C2 - 16228000
AN - SCOPUS:27644590509
VL - 37
SP - 1247
EP - 1252
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 11
ER -