Extending the clinical heterogeneity of iodide transport defect (ITD): a novel mutation R124H of the sodium/iodide symporter gene and review of genotype-phenotype correlations in ITD.

Context: Iodide transport defect (ITD) is an autosomal recessive disorder resulting in varying degrees of congenital hypothyroidism (CH) with goiter and low or absent radioiodide uptake (RIUT), as determined by thyroid scintigraphy, and low iodide saliva to plasma ratio. Defects of the sodium/iodide symporter gene (NIS) have been shown to cause ITD. Objective: We describe molecular studies of NIS in a patient with ITD and genotype-phenotype correlation analysis in 31 patients with NIS defects reported worldwide. Design: NIS sequencing and functional studies of the new NIS mutation in vitro were performed. Results: In a newborn with symptomatic CH and a large goiter, thyroid scintigraphy showed no RIUT (0%). NIS sequencing identified the new homozygous mutation, R124H, in exon 2. This mutation was associated with abolition of iodide uptake in vitro when transfected in COS-7 cells. Immunocytochemical studies documented correct targeting of the mutated protein to the plasma membrane of transfected cells. Gen...