Hypothyroidism in a Brazilian kindred due to iodide trapping defect caused by a homozygous mutation in the sodium/iodide symporter gene
- PMID: 9388506
- DOI: 10.1006/bbrc.1997.7594
Hypothyroidism in a Brazilian kindred due to iodide trapping defect caused by a homozygous mutation in the sodium/iodide symporter gene
Abstract
A 36 year old man with a large goiter was suspected of having iodide (I-) transport defect based on low thyroidal and salivary gland radioiodide uptake. Thyroid surgery was performed, because thyroid cytology could not exclude a malignancy. Sequencing of the entire Na+/I- symporter (NIS) cDNA derived from thyroidal mRNA revealed a homozygous substitution of the normal cytosine in nucleotide (nt) 1163 with an adenine, resulting in a stop (TGA) at codon 272. This nonsense mutation produces a truncated NIS with undetectable I- transport activity when expressed into COS-7 cells. Genotyping confirmed that the propositus was homozygous for the mutation whereas his unaffected mother, son, and paternal aunt were heterozygous. This nt substitution was not detected in any of 50 normal individuals, ruling out a polymorphism. While the homozygous mutant NIS-272X causes congenital hypothyroidism, expression of one normal allele in the heterozygote (C272X) is sufficient to maintain active thyroidal I- uptake and function.
Similar articles
-
Congenital hypothyroidism due to mutations in the sodium/iodide symporter. Identification of a nonsense mutation producing a downstream cryptic 3' splice site.J Clin Invest. 1998 Mar 1;101(5):1028-35. doi: 10.1172/JCI1504. J Clin Invest. 1998. PMID: 9486973 Free PMC article.
-
Novel, missense and loss-of-function mutations in the sodium/iodide symporter gene causing iodide transport defect in three Japanese patients.J Clin Endocrinol Metab. 1998 Sep;83(9):3373-6. doi: 10.1210/jcem.83.9.5245. J Clin Endocrinol Metab. 1998. PMID: 9745458
-
A novel mutation in the sodium/iodide symporter gene in the largest family with iodide transport defect.J Clin Endocrinol Metab. 1999 Sep;84(9):3248-53. doi: 10.1210/jcem.84.9.5971. J Clin Endocrinol Metab. 1999. PMID: 10487695
-
Mutations in the sodium/iodide symporter (NIS) gene as a cause for iodide transport defects and congenital hypothyroidism.Biochimie. 1999 May;81(5):469-76. doi: 10.1016/s0300-9084(99)80097-2. Biochimie. 1999. PMID: 10403177 Review.
-
Congenital hypothyroidism caused by new mutations in the thyroid oxidase 2 (THOX2) gene.Clin Endocrinol (Oxf). 2006 Dec;65(6):810-5. doi: 10.1111/j.1365-2265.2006.02672.x. Clin Endocrinol (Oxf). 2006. PMID: 17121535 Review.
Cited by
-
Novel Compound Heterozygous Pathogenic Mutations of SLC5A5 in a Chinese Patient With Congenital Hypothyroidism.Front Endocrinol (Lausanne). 2021 Mar 19;12:620117. doi: 10.3389/fendo.2021.620117. eCollection 2021. Front Endocrinol (Lausanne). 2021. PMID: 33815280 Free PMC article.
-
Na+ coordination at the Na2 site of the Na+/I- symporter.Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):E5379-88. doi: 10.1073/pnas.1607231113. Epub 2016 Aug 25. Proc Natl Acad Sci U S A. 2016. PMID: 27562170 Free PMC article.
-
Clinical Significance of Thyroid-Stimulating Hormone Receptor Gene Mutations and/or Sodium-Iodine Symporter Gene Overexpression in Indeterminate Thyroid Fine Needle Biopsies.Front Endocrinol (Lausanne). 2018 Sep 25;9:566. doi: 10.3389/fendo.2018.00566. eCollection 2018. Front Endocrinol (Lausanne). 2018. PMID: 30319546 Free PMC article.
-
Genetic disorders coupled to ROS deficiency.Redox Biol. 2015 Dec;6:135-156. doi: 10.1016/j.redox.2015.07.009. Epub 2015 Jul 17. Redox Biol. 2015. PMID: 26210446 Free PMC article. Review.
-
Genetics and phenomics of hypothyroidism and goiter due to NIS mutations.Mol Cell Endocrinol. 2010 Jun 30;322(1-2):56-63. doi: 10.1016/j.mce.2010.02.007. Epub 2010 Feb 12. Mol Cell Endocrinol. 2010. PMID: 20153805 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases
Research Materials