A homozygous missense mutation of the sodium/iodide symporter gene causing iodide transport defect

被引:69
作者
Matsuda, A [1 ]
Kosugi, S [1 ]
机构
[1] Kyoto Univ, Sch Med, Dept Lab Med, Sakyo Ku, Kyoto 60601, Japan
关键词
D O I
10.1210/jc.82.12.3966
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 A-->C 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 Thr(354)-->Pro 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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页码:3966 / 3971
页数:6
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