<b>Background:</b> Perchlorate, thiocyanate, and nitrate can block iodide transport at the sodium iodide symporter (NIS) and this can subsequently lead to decreased thyroid hormone production and hypothyroidism.
We demonstrate the mutation of residue Gly93 of hNIS to a larger amino acid expels the side chain of a critical tryptophan residue (Trp255) into the interior of the binding pocket, partially occluding the iodide binding site and reducing iodide affinity, which is consistent with previous reports associating mutation of this residue with iodide uptake deficiency and hypothyroidism.
Biallelic mutations in the NIS gene lead to a congenital iodide transport defect, an autosomal recessive condition characterized by hypothyroidism, goiter, low thyroid iodide uptake, and a low saliva/plasma iodide ratio.
This is consequential to intranodular iodide deficiency, mainly due to cytoplasmic sodium iodide symporter localization, and portrays the CTN as an activated proliferating lesion with an intranodular hypothyroid milieu.
Genotype-phenotype correlation analysis showed that the onset of hypothyroidism occurred during the neonatal period with four NIS mutations (neonatal onset of hypothyroidism genotype), during infancy with three NIS mutations (infancy onset of hypothyroidism genotype), and during childhood with three NIS mutations (childhood onset of hypothyroidism genotype).
The hypothyroidism was associated with increased mRNA levels of the sodium-iodide symporter, an increase partly due to a direct effect of IL-12 on the thyrocyte.
A defect in the NIS (iodide trapping defect) can result in hypothyroidism, the severity of which is variable and influenced, in part, by the amount of iodine supply.