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A Homozygous Missense Mutation of the Sodium/Iodide Symporter Gene Causing Iodide Transport Defect¹

Department of Laboratory Medicine, Kyoto University School of Medicine, Kyoto 606–01, Japan

Address all correspondence and requests for reprints to: Dr. Shinji Kosugi, Department of Laboratory Medicine, Kyoto University School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606–01, Japan. E-mail: kosugi{at}kuhp.kyoto-u.ac.jp

Iodide transport defect is a disorder characterized by an inability of the thyroid to maintain an iodide concentration difference between the plasma and the thyroid. The recent cloning of the sodium/iodide symporter (NIS) gene enabled us to characterize the NIS gene in this disorder. We identified a homozygous missense mutation of AC at nucleotide +1060 in NIS complementary DNA in a male patient who was born from consanguineous marriage, had a huge goiter, and lacked the ability to accumulate iodide but was essentially euthyroid. The mutation results in an amino acid replacement of Thr³⁵⁴Pro in the middle of the ninth transmembrane domain. COS-7 cells transfected with the mutant NIS complementary DNA showed markedly decreased iodide uptake, confirming that this mutation was the direct cause of the disorder in the patient. Northern analysis of thyroid ribonucleic acid revealed that NIS messenger ribonucleic acid level was markedly increased (>100-fold) compared with that in the normal thyroid, suggesting possible compensation by overexpression.

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