Mutations in the sodium/iodide symporter (NIS) gene as a cause for iodide transport defects and congenital hypothyroidism

Biochimie ◽  
1999 ◽  
Vol 81 (5) ◽  
pp. 469-476 ◽  
Author(s):  
Joachim Pohlenz ◽  
Samuel Refetoff
Keyword(s):  
Congenital Hypothyroidism ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Transport ◽  
Nis Gene

scholarly journals The importance of sodium/iodide symporter (NIS) for thyroid cancer management

2007 ◽  
Vol 51 (5) ◽  
pp. 672-682 ◽  
Author(s):  
Denise P. Carvalho ◽  
Andrea C.F. Ferreira
Keyword(s):  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Therapeutic Tool ◽  
Iodide Transport ◽  
Cancer Management ◽  
Thyroid Hormone Biosynthesis ◽  
Nis Gene ◽  
Hormone Biosynthesis ◽  
Tumoral Cells

The thyroid gland has the ability to uptake and concentrate iodide, which is a fundamental step in thyroid hormone biosynthesis. Radioiodine has been used as a diagnostic and therapeutic tool for several years. However, the studies related to the mechanisms of iodide transport were only possible after the cloning of the gene that encodes the sodium/iodide symporter (NIS). The studies about the regulation of NIS expression and the possibility of gene therapy with the aim of transferring NIS gene to cells that normally do not express the symporter have also become possible. In the majority of hypofunctioning thyroid nodules, both benign and malignant, NIS gene expression is maintained, but NIS protein is retained in the intracellular compartment. The expression of NIS in non-thyroid tumoral cells in vivo has been possible through the transfer of NIS gene under the control of tissue-specific promoters. Apart from its therapeutic use, NIS has also been used for the localization of metastases by scintigraphy or PET-scan with 124I. In conclusion, NIS gene cloning led to an important development in the field of thyroid pathophysiology, and has also been fundamental to extend the use of radioiodine for the management of non-thyroid tumors.

scholarly journals Mutation screening of the sodium iodide symporter gene in a cohort of 105 China patients with congenital hypothyroidism

2014 ◽  
Vol 58 (8) ◽  
pp. 828-832 ◽  
Author(s):  
Chunyun Fu ◽  
Shaoke Chen ◽  
Rongyu Chen ◽  
Xin Fan ◽  
Jingsi Luo ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Sodium Iodide ◽  
Mutation Screening ◽  
Gene Mutations ◽  
Sodium Iodide Symporter ◽  
Blood Leukocytes ◽  
Autonomous Region ◽  
Guangxi Zhuang Autonomous Region ◽  
Missense Variation ◽  
Nis Gene

Objective Dyshormonogenetic congenital hypothyroidism (CH) was reported to be associated with a mutation in the sodium iodide symporter (NIS) gene. The present study was undertaken in the Guangxi Zhuang Autonomous Region of China, to determine the nature and frequency of NIS gene mutations among patients with CH due to dyshormonogenesis. Subjects and methods: Blood samples were collected from 105 dyshormonogenetic CH patients in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes. All exons of the NIS gene together with their exon-intron boundaries were screened by next-generation sequencing. Results Two silent variations (T221T and T557T) and one missense variation (M435L), as well as two polymorphisms (rs200587561 and rs117626343) were found. Conclusions Our results indicate that the NIS mutation rate is very low in the Guangxi Zhuang Autonomous Region, China, and it is necessary to study mutations of other genes that have major effects on thyroid dyshormonogenesis and have not as yet been studied in this population.

scholarly journals Congenital Hypothyroidism Caused by a PAX8 Gene Mutation Manifested as Sodium/Iodide Symporter Gene Defect

2010 ◽  
Vol 2010 ◽  
pp. 1-3 ◽  
Author(s):  
Wakako Jo ◽  
Katsura Ishizu ◽  
Kenji Fujieda ◽  
Toshihiro Tajima
Keyword(s):  
Thyroid Gland ◽  
Congenital Hypothyroidism ◽  
Sodium Iodide ◽  
Present Report ◽  
Sodium Iodide Symporter ◽  
Loss Of Function ◽  
Laboratory Findings ◽  
Iodide Transport ◽  
Transport Defect ◽  
Pax8 Gene

Loss-of-function mutations of the PAX8 gene are considered to mainly cause congenital hypothyroidism (CH) due to thyroid hypoplasia. However, some patients with PAX8 mutation have demonstrated a normal-sized thyroid gland. Here we report a CH patient caused by a PAX8 mutation, which manifested as iodide transport defect (ITD). Hypothyroidism was detected by neonatal screening and L-thyroxine replacement was started immediately. Although I scintigraphy at 5 years of age showed that the thyroid gland was in the normal position and of small size, his iodide trapping was low. The ratio of the saliva/plasma radioactive iodide was low. He did not have goiter; however laboratory findings suggested that he had partial ITD. Gene analyses showed that the sodium/iodide symporter (NIS) gene was normal; instead, a mutation in the PAX8 gene causing R31H substitution was identified. The present report demonstrates that individuals with defective PAX8 can have partial ITD, and thus genetic analysis is useful for differential diagnosis.

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

1997 ◽  
Vol 82 (12) ◽  
pp. 3966-3971
Author(s):  
Akira Matsuda ◽  
Shinji Kosugi
Keyword(s):  
Missense Mutation ◽  
Ribonucleic Acid ◽  
Sodium Iodide ◽  
Northern Analysis ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Complementary Dna ◽  
Homozygous Missense Mutation ◽  
Iodide Transport ◽  
Nis Gene

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 Thr354→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.

Novel Sodium/Iodide Symporter Compound Heterozygous Pathogenic Variants Causing Dyshormonogenic Congenital Hypothyroidism

Thyroid ◽  
2019 ◽  
Vol 29 (7) ◽  
pp. 1023-1026 ◽  
Author(s):  
Mariano Martín ◽  
Carlos Eduardo Bernal Barquero ◽  
Romina Celeste Geysels ◽  
Patricia Papendieck ◽  
Victoria Peyret ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Sodium Iodide ◽  
Compound Heterozygous ◽  
Sodium Iodide Symporter ◽  
Pathogenic Variants

scholarly journals Decreased Expression of Thyroglobulin and Sodium Iodide Symporter Genes in Hashimoto’s Thyroiditis

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Anna Popławska-Kita ◽  
Beata Telejko ◽  
Katarzyna Siewko ◽  
Maria Kościuszko-Zdrodowska ◽  
Natalia Wawrusewicz-Kurylonek ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Hashimoto’S Thyroiditis ◽  
Sodium Iodide ◽  
Interleukin 1 ◽  
Thyroid Volume ◽  
Needle Aspiration ◽  
Hashimoto's Thyroiditis ◽  
Sodium Iodide Symporter ◽  
Thyroid Cells ◽  
Iodide Transport

Aim. The aim of the study was to compare the expression of sodium iodide symporter (NIS), thyroglobulin (Tg), tumor necrosis factor-α(TNFα), and interleukin-1βgenes in patients with Hashimoto’s thyroiditis (HT) and healthy individuals.Subjects and Methods.Thyroid cells were obtained from 39 patients with HT and 15 controls by an ultrasound guided fine needle aspiration biopsy.Results. The patients with HT had lower Tg and NIS mRNA (P=0.002andP=0.001, resp.), as well as higher TNFαmRNA expression (P=0.049) than the controls. In the HT group Tg mRNA expression correlated positively with NIS mRNA expression (R=0.739,P=0.0001) and thyroid volume (R=0.465,P=0.0005), as well as negatively with TNFαmRNA expression (R=-0.490,P=0.001) and anti-peroxidase antibodies (TPOAb) level (R=-0.482,P=0.0002), whereas NIS mRNA expression correlated positively with thyroid volume (R=0.319,P=0.02), as well as negatively with TNFαmRNA expression (R=-0.529,P=0.0006) and TPOAb level (R=-0.422,P=0.001).Conclusions.Our results suggest that decreased Tg and NIS expression in thyroid cells may result in reduced active iodide transport and reduced thyroid volume in patients with HT.

scholarly journals Application of 188Rhenium as an Alternative Radionuclide for Treatment of Prostate Cancer after Tumor-Specific Sodium Iodide Symporter Gene Expression

2007 ◽  
Vol 92 (11) ◽  
pp. 4451-4458 ◽  
Author(s):  
Michael J. Willhauck ◽  
Bibi-Rana Sharif Samani ◽  
Franz-Josef Gildehaus ◽  
Ingo Wolf ◽  
Reingard Senekowitsch-Schmidtke ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Therapeutic Effect ◽  
Half Life ◽  
Sodium Iodide ◽  
Specific Antigen ◽  
Volume Reduction ◽  
Sodium Iodide Symporter ◽  
Nis Gene

Abstract Context: We reported recently the induction of iodide accumulation in prostate cancer cells (LNCaP) by prostate-specific antigen promoter-directed sodium iodide symporter (NIS) expression that allowed a significant therapeutic effect of 131iodine (131I). These data demonstrated the potential of the NIS gene as a novel therapeutic gene, although in some extrathyroidal tumors, therapeutic efficacy may be limited by rapid iodide efflux due to a lack of iodide organification. Objective: In the current study, we therefore studied the potential of 188rhenium (188Re), as an alternative radionuclide, also transported by NIS, with a shorter half-life and higher energy β-particles than 131I. Results: NIS-transfected LNCaP cells (NP-1) concentrated 8% of the total applied activity of 188Re as compared with 16% of 125I, which was sufficient for a therapeutic effect in an in vitro clonogenic assay. γ-Camera imaging of NP-1 cell xenografts in nude mice revealed accumulation of 8–16% injected dose (ID)/g 188Re (biological half-life 12.9 h), which resulted in a 4.7-fold increased tumor absorbed dose (450 mGy/MBq) for 188Re as compared with 131I. After application of 55.5 MBq 131I or 188Re, smaller tumors showed a similar average volume reduction of 86%, whereas in larger tumors volume reduction was significantly increased from 73% after 131I treatment to 85% after application of 188Re. Conclusion: Although in smaller prostate cancer xenografts both radionuclides seemed to be equally effective after prostate-specific antigen promoter-mediated NIS gene delivery, a superior therapeutic effect has been demonstrated for 188Re in larger tumors.

scholarly journals Regulation of the sodium iodide symporter by iodide in FRTL-5 cells

2001 ◽  
pp. 139-144 ◽  
Author(s):  
PH Eng ◽  
GR Cardona ◽  
MC Previti ◽  
WW Chin ◽  
LE Braverman
Keyword(s):  
Sodium Iodide ◽  
Cell Model ◽  
High Plasma ◽  
Northern Analysis ◽  
Thyroid Cell ◽  
Transcriptional Level ◽  
Sodium Iodide Symporter ◽  
Iodide Transport ◽  
Excess Iodide

OBJECTIVE: The acute decrease in iodide organification in the thyroid in response to excess iodide is termed the acute Wolff-Chaikoff effect and normal organification resumes in spite of continued high plasma iodide concentrations (escape from the acute Wolff-Chaikoff effect). We have recently reported that large doses of iodide given to rats chronically decrease the sodium/iodide symporter (NIS) mRNA and protein, suggesting that escape is due to a decrease in NIS and subsequent iodide transport. We have now studied the effect of excess iodide on NIS in FRTL-5 cells to further explore the mechanisms whereby excess iodide decreases NIS. DESIGN: FRTL-5 cells were employed and were incubated in the presence or absence of various concentrations of iodide. NIS mRNA and protein and the turnover of NIS were assessed. METHODS: NIS mRNA was measured by Northern analysis, NIS protein by Western analysis and NIS turnover by pulse-chase labeling experiments. RESULTS: Iodide (10(-) mol/l) had no effect on NIS mRNA in FRTL-5 cells at 24 and 48 h compared with cells cultured in the absence of iodide. However, excess iodide decreased NIS protein by 50% of control values at 24 h and by 70% at 48 h. This effect of iodide was dose dependent. Pulse-chase experiments demonstrated that there was no effect of iodide on new NIS protein synthesis and that the turnover of NIS protein in the presence of iodide was 27% faster than in the absence of added iodide. CONCLUSIONS: Excess iodide does not decrease NIS mRNA in FRTL-5 cells but does decrease NIS protein, suggesting that in this in vitro thyroid cell model iodide modulates NIS, at least in part, at a post-transcriptional level. This iodide-induced decrease in NIS protein appears to be due, at least partially, to an increase in NIS protein turnover.

scholarly journals Na(+)/I(-) symporter and Pendred syndrome gene and protein expressions in human extra-thyroidal tissues

2001 ◽  
pp. 297-302 ◽  
Author(s):  
L Lacroix ◽  
C Mian ◽  
B Caillou ◽  
M Talbot ◽  
S Filetti ◽  
...  
Keyword(s):  
Protein Expression ◽  
Real Time ◽  
Quantitative Pcr ◽  
Thick Ascending Limb ◽  
Sodium Iodide Symporter ◽  
Pendred Syndrome ◽  
Real Time Quantitative Pcr ◽  
Iodide Transport ◽  
Gene And Protein Expression ◽  
Nis Gene

OBJECTIVE: The expression of two recently identified iodide transporters, namely the sodium/iodide symporter (NIS) and pendrin, the product of the gene responsible for the Pendred syndrome (PDS), was studied in a series of various extra-thyroidal human tissues, and especially in those known to concentrate iodide. METHODS: To this end, we used real-time kinetic quantitative PCR to detect NIS and PDS transcripts and immunohistochemistry for the analysis of their protein products. RESULTS: NIS gene and protein expression was detected in most tissues known to concentrate iodine, and particularly in salivary glands and stomach. In contrast, PDS gene expression was restricted to a few tissues, such as kidney and Sertoli cells. Interestingly, in kidney, pendrin immunostaining was detected at the apical pole of epithelial cells of the thick ascending limb of the Henle's loop and of the distal convoluted tubule. CONCLUSION: This study provides new insights on the localization and expression of two genes involved in iodide transport and emphasizes the interest of combining real-time quantitative PCR and immunohistochemistry for the comparison of gene and protein expression in tissues.

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