Abstract
Mutations in the cell membrane thyroid hormone (TH) transporter monocarboxylate transporter (MCT) 8 produce severe neuropsychomotor defects and characteristic thyroid function test (TFT) abnormalities. Two children with mild neurological phenotypes and normal TFTs were found to harbor
MCT8
gene variants of unknown significance (VUS), MCT8-R388Q that occurred
de novo,
and MCT8-Q212E. Normal TH transport and action in fibroblasts of MCT8-R388Q was demonstrated in a novel nonradioactive functional assay measuring the intracellular TH availability after L-T3 treatment. No genotype–phenotype correlation was found in additional family members carrying MCT8-Q212E. For the field of MCT8 deficiency, it is important to assess the significance of
MCT8
gene VUS.
