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

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.

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

Biochimie ◽

10.1016/s0300-9084(99)80097-2 ◽

1999 ◽

Vol 81 (5) ◽

pp. 469-476 ◽

Cited By ~ 41

Author(s):

Joachim Pohlenz ◽

Samuel Refetoff

Keyword(s):

Congenital Hypothyroidism ◽

Sodium Iodide ◽

Sodium Iodide Symporter ◽

Iodide Transport ◽

Nis Gene

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Mutation screening of the thyroid peroxidase gene in a cohort of 55 Portuguese patients with congenital hypothyroidism

Acta Endocrinologica ◽

10.1530/eje.1.01826 ◽

2005 ◽

Vol 152 (2) ◽

pp. 193-198 ◽

Cited By ~ 35

Author(s):

Carina Rodrigues ◽

Paula Jorge ◽

José Pires Soares ◽

Isaura Santos ◽

Regina Salomão ◽

...

Keyword(s):

Congenital Hypothyroidism ◽

Mutation Screening ◽

Gene Mutations ◽

Human Thyroid ◽

Thyroid Peroxidase ◽

Molecular Testing ◽

Missense Mutations ◽

Human Thyroid Peroxidase ◽

Iodide Organification Defect ◽

Organification Defect

Objective: Defects in the human thyroid peroxidase (TPO) gene are reported to be one of the causes of congenital hypothyroidism (CH) due to a total iodide organification defect. The aim of the present study was to determine the nature and frequency of TPO gene mutations in patients with CH, characterised by elevated TSH levels and orthotopic thyroid gland, identified in the Portuguese National Neonatal Screening Programme. Subjects and methods: The sample comprised 55 patients, from 53 unrelated families, with follow-up in the endocrinology clinics of the treatment centres of Porto and Lisbon. Mutation screening in the TPO gene (exons 1–17) was performed by single-strand conformational analysis followed by sequencing of fragments with abnormal migration patterns. Results: Eight different mutations were detected in 13 patients (seven homozygotes and six compound heterozygotes). Novel mutations included three missense mutations, namely 391T > C (S131P), 1274A > G (N425S) and 2512T > A (C838S), as well as the predictable splice mutation 2748G > A (Q916Q/spl?). The undocumented polymorphism 180-47A > C was also detected. Conclusion: The results are in accordance with previous observations confirming the genetic heterogeneity of TPO defects. The proportion of patients in which the aetiology was determined justifies the implementation of this molecular testing in our CH patients with dyshormonogenesis.

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

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302007000500004 ◽

2007 ◽

Vol 51 (5) ◽

pp. 672-682 ◽

Cited By ~ 36

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.

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

Thyroid ◽

10.1089/thy.2019.0046 ◽

2019 ◽

Vol 29 (7) ◽

pp. 1023-1026 ◽

Cited By ~ 4

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

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Molecular Spectrum of α- and β-Globin Gene Mutations Detected in the Population of Guangxi Zhuang Autonomous Region, People's Republic of China

Hemoglobin ◽

10.3109/03630269.2010.547429 ◽

2011 ◽

Vol 35 (1) ◽

pp. 28-39 ◽

Cited By ~ 25

Author(s):

Chen-Guang Zheng ◽

Ming Liu ◽

Juan Du ◽

Ke Chen ◽

Yige Yang ◽

...

Keyword(s):

Globin Gene ◽

Gene Mutations ◽

Molecular Spectrum ◽

People’S Republic Of China ◽

People's Republic Of China ◽

Autonomous Region ◽

Republic Of China ◽

Guangxi Zhuang Autonomous Region

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-0402 ◽

2007 ◽

Vol 92 (11) ◽

pp. 4451-4458 ◽

Cited By ~ 37

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.

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