These data suggest an iodide organification defect in 17 cases; an iodide transport defect (NIS defect) in three, probable TSH resistance in 10, and a TG synthesis defect in two cases.
We described a novel mutation in the 5'-untranslated region of the NIS gene in a newborn with congenital hypothyroidism bearing a clinical ITD phenotype.
Iodide transport defect (ITD) is an infrequent condition associated with congenital dyshormonogenetic goiter due to mutations in the Na(+)/I(-) symporter (NIS) gene transmitted in an autosomal recessive manner.
The study of NIS mutations as the molecular basis of ITD has not only yielded extremely valuable structure/function information on NIS, but has also provided an important tool for preclinical diagnosis and genetic counseling of ITD patients.
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.
We describe molecular studies of NIS in a patient with ITD and genotype-phenotype correlation analysis in 31 patients with NIS defects reported worldwide.
COS-7 cells transfected with a vector expressing the mutant del-(439-443) NISfailed to concentrate iodide, suggesting that the mutation was the direct cause of the ITD in this patient.
It is now possible to use gene diagnostics of this unique NIS mutation to identify patients with congenital hypothyroidism due to an iodide transport defect in this family and to determine the carrier state of potential parents for genetic counseling and arranging rapid and early diagnosis of their infants.