High prevalence of T354P sodium/iodide symporter gene mutation in Japanese patients with iodide transport defect who have heterogeneous clinical pictures.
High prevalence of T354P sodium/iodide symporter gene mutation in Japanese patients with iodide transport defect who have heterogeneous clinical pictures.
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在具有异质临床表现的碘转运缺陷日本患者中，T354P 钠/碘同向转运蛋白基因突变的患病率较高。
DOI：
--
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发表时间：
1998
影响因子：
5.8
通讯作者：
S. Jhiang
中科院分区：
文献类型：
--
作者：
S. Kosugi;Y. Sato;A. Matsuda;Y. Ohyama;K. Fujieda;H. Inomata;T. Kameya;O. Isozaki;S. Jhiang
在两名不相关的日本碘转运缺陷患者的纯合子状态中发现了Na+/I-同向转运体（NIS）基因T354 P [Thr 354-->Pro（ACA-->CCA）]的错义和功能缺失突变。在这项研究中，我们已经确定了纯合子T354 P NIS种系突变在7名日本患者，包括以前报道的，从五个无关的家庭。在这7名患者中，未发现NIS基因编码区和外显子-内含子边界的其他核苷酸变化。这些结果表明，T354 P突变在日本患者中普遍存在。虽然这7例患者有相同的NIS突变，T354 P，显着的异质性，在临床表现，特别是有关甲状腺肿和甲状腺功能减退症，其中注意到。因此，另一个因素，但不是NIS突变的性质，可能解释了碘转运缺陷患者的临床异质性。我们以前曾报道过，NIS信使核糖核酸显着增加，在甲状腺的纯合子T354 P突变的患者。在这项研究中，我们证明了NIS蛋白在患者的甲状腺显着增加（约10倍），通过蛋白质印迹分析的完整的膜蛋白使用的抗体对C-末端肽的人NIS。此外，我们通过免疫组织化学染色显示T354 P突变NIS蛋白在患者甲状腺细胞的基底和侧质膜中过表达。
A missense and loss of function mutation of the Na+/I- symporter (NIS) gene, T354P [Thr354-->Pro (ACA-->CCA)], was found in the homozygous state in two unrelated Japanese patients with iodide transport defect. In this study we have identified the homozygous T354P NIS germline mutation in seven Japanese patients, including one previously reported, from five unrelated families. No other nucleotide changes were found in the coding regions and the exon-intron boundaries of the NIS gene in these seven patients. These results suggest a common prevalence of the T354P mutation in Japanese patients. Although these seven patients have the identical NIS mutation, T354P, marked heterogeneity in clinical pictures, especially concerning goiter and hypothyroidism, were noted among them. Therefore, another factor(s), but not the nature of the NIS mutation, may account for the clinical heterogeneity among patients with the iodide transport defect. We have previously reported that the NIS messenger ribonucleic acid was markedly increased in the thyroid of a patient with the homozygous T354P mutation. In this study we demonstrated that the NIS proteins in the patients' thyroids were significantly increased (approximately 10-fold) by Western blot analysis of integral membrane proteins using an antibody against the C-terminal peptide of the human NIS. Furthermore, we showed by immunohistochemical staining that the T354P mutant NIS proteins were overexpressed in the basal and lateral plasma membranes of patients' thyrocytes.
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由于钠/碘同向转运蛋白突变而导致的先天性甲状腺功能减退症。
DOI：
10.1172/jci1504
发表时间：
1998
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Pohlenz,J;Rosenthal,IM;Weiss,RE;Jhiang,SM;Burant,C;Refetoff,S
通讯作者：
Refetoff,S
影响因子：
4.8
作者：
P. Smanik;Kwon-Yul Ryu;Karl S. Theil;Ernest L. Mazzaferri;S. Jhiang
通讯作者：
P. Smanik;Kwon-Yul Ryu;Karl S. Theil;Ernest L. Mazzaferri;S. Jhiang
DOI：
10.1006/bbrc.1996.1358
发表时间：
1996-09-13
影响因子：
3.1
作者：
Smanik, PA;Liu, Q;Jhiang, SM
通讯作者：
Jhiang, SM
DOI：
10.1073/pnas.94.11.5568
发表时间：
1997-05-27
影响因子：
11.1
作者：
Levy, O;Dai, G;Carrasco, N
通讯作者：
Carrasco, N
DOI：
10.1006/bbrc.1997.7594
发表时间：
1997-11-17
影响因子：
3.1
作者：
Pohlenz, J;MedeirosNeto, G;Refetoff, S
通讯作者：
Refetoff, S