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Recurrent T354P Mutation of the Na⁺/I^- Symporter in Patients with Iodide Transport Defect¹

Department of Laboratory Medicine, D2 (H.F., K.T., N.A.) and Department of Pediatrics, D5 (K.M., T.H., S.O.), Osaka University Medical School, Osaka 565-0871, Japan; Nose Clinic (O.N.), Osaka 530, Japan; and Department of Pediatrics, Himeji Red Cross Hospital (S.K.), Hyogo 670, Japan

Address all correspondence and requests for reprints to: Tatsumi Ke-ita, Department of Laboratory Medicine, D2, Osaka University Medical School, Suita-shi Yamada-oka 2–2, Osaka 565-0871, Japan. E-mail: tatsumi{at}labo.med.osaka-u.ac.jp

Iodide transport defect (ITD) is a rare disorder causing congenital hypothyroidism. We previously reported that homozygous T354P mutation in the sodium/iodide symporter (NIS) gene caused ITD. To clarify the prevalence of this mutation, artificial substitution introducing PCR followed by restriction enzyme analysis was developed as a rapid screening method to detect the T354P mutation. Three apparently unrelated families with ITD, one patient with low thyroidal ^99mTc pertechnetate (^99mTcO₄^-) uptake and 52 healthy controls (104 alleles) were analyzed for this mutation. All families with ITD harbored the mutation, suggesting that T354P is a recurrent mutation and a major cause of ITD. This was not a widespread mutation, because it was not detected in the 52 unrelated normal controls. Because two cases with homozygous T354P mutation developed multinodular goiters within their second decade of life though they had been maintained in euthyroid state, homozygous T354P mutation alone and/or low intrathyroidal iodide and high serum TSH level in early life might account for tumorigenesis. The patient with low thyroidal ^99mTcO₄^- 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.

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