Syndromes of Reduced Sensitivity to Thiroid Hormone Genettic Defects in Hormone Receptors, Gell Transporters and Deiodination
Issue: 4/2010
Author: Samuel Refetoff and Alexandra M. Dumitrescu
Abstract:
At least six major steps are required for secreted thyroid hormone (TH) to exert its action on target tissues. Mutations interfering with three of these steps have been so far identified and are the subject of this communication.
The first recognized defect, causing resistance to TH, involves the TH receptor ? gene and carries the acronym, RTH. Occurring in ~1 of 40,000 newborn, affected subjects belonging to 339 families surpass 1,000. The gene defect remains unknown in 15% of subjects with RTH. Two novel syndromes causing reduced sensitivity to TH were recently identified. One, producing severe psychomotor defects in more than 150 males from 57 families, is caused by mutations in the cell-membrane transporter of TH, MCT8. The second defect, affecting the intracellular metabolism of TH is caused by mutations in the SECISBP2 gene required for the synthesis of selenoproteins, including TH deiodinases.
Keywords: Resistance to thyroid hormone, T3-beta gene, TH deiodinases, cell-membrane transporter of thyroid hormones.
