RECURRENT T354P MUTATION OF THE NA+ I- SYMPORTER IN PATIENTS WITH IODIDE TRANSPORT DEFECTS/

Iodide transport defect (ITD) is a rare disorder causing congenital hy pothyroidism, We previously reported that homozygous T354P mutation in the sodium/iodide symporter (NIS) gene caused ITD. To clarify the pre valence of this mutation, artificial substitution introducing PCR foll owed by restriction enzyme analysis was developed as a rapid screening method to detect the T354P mutation. Three apparently unrelated famil ies with ITD, one patient with low thyroidal Tc-99m pertechnetate ((Tc O4-)-Tc-99m) uptake and 52 healthy controls (104 alleles) were analyze d for this mutation. All families with ITD harbored the mutation, sugg esting that T354P is a recurrent mutation and a major cause of ITD. Th is was not a widespread mutation, because it was not detected in the 5 2 unrelated normal controls. Because two cases with homozygous T354P m utation developed multinodular goiters within their second decade of l ife though they had been maintained in euthyroid state, homozygous T35 4P mutation alone and/or low intrathyroidal iodide and high serum TSH level in early life might account for tumorigenesis. The patient with low thyroidal (TcO4-)-Tc-99m uptake did not harbor the T354P mutation. Because familial hypocalciuric hypercalcemia was also present in this family, a possibility of the combined abnormality of TSH receptor and calcium functions, which includes an abnormality around the G protein , may be examined further.