ArticleThe Journal of clinical investigation1998
Congenital hypothyroidism due to mutations in the sodium/iodide symporter. Identification of a nonsense mutation producing a downstream cryptic 3' splice site.
Article in The Journal of clinical investigation, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 121 citations in OpenAlex.
- New Insights into Iodide Transport Defects (ITDs) from the Characterization of a Heterozygous NIS Missense Variant (p.G288S) Identified in a Family with Thyroid Dysfunction During Pregnancy.International journal of molecular sciences · 2026Article
- Silent but Not Harmless: A SynonymousFrontiers in endocrinology · 2022Article
- Transcriptomic Signature of Human Embryonic Thyroid Reveals Transition From Differentiation to Functional Maturation.Frontiers in cell and developmental biology · 2021Article
- Transcription factor GLIS3: Critical roles in thyroid hormone biosynthesis, hypothyroidism, pancreatic beta cells and diabetes.Pharmacology & therapeutics · 2020Review
- Review
- Mapping of Ion and Substrate Binding Sites in Human Sodium Iodide Symporter (hNIS).Journal of chemical information and modeling · 2020Article
- Relevance of solute carrier family 5 transporter defects to inherited and acquired human disease.Journal of applied genetics · 2019Review
- Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism.JCI insight · 2018Article
- Euthyroid athyroxinemia - a novel endocrine syndrome.Endocrinology, diabetes & metabolism case reports · 2017Article
- Na+ coordination at the Na2 site of the Na+/I- symporter.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Congenital hypothyroidism and thyroid dyshormonogenesis: a case report of siblings with a newly identified mutation in thyroperoxidase.Journal of pediatric endocrinology & metabolism : JPEM · 2016Article
- Genetic disorders coupled to ROS deficiency.Redox biology · 2015Review
- TRANSCRIPTION FACTOR GLI-SIMILAR 3 (GLIS3): IMPLICATIONS FOR THE DEVELOPMENT OF CONGENITAL HYPOTHYROIDISM.Journal of endocrinology, diabetes & obesity · 2014Article
- Determination of the consequences of VHL mutations on VHL transcripts in renal cell carcinoma.International journal of oncology · 2012Article
- Genetic causes of congenital hypothyroidism due to dyshormonogenesis.Current opinion in pediatrics · 2011Review
- Genetics and phenomics of hypothyroidism and goiter due to NIS mutations.Molecular and cellular endocrinology · 2010Review
- Congenital Hypothyroidism Caused by a PAX8 Gene Mutation Manifested as Sodium/Iodide Symporter Gene Defect.Journal of thyroid research · 2010Article
- Genomic features defining exonic variants that modulate splicing.Genome biology · 2010Article
- Molecular characterization of V59E NIS, a Na+/I- symporter mutant that causes congenital I- transport defect.Endocrinology · 2008Article
- Inherited epithelial transporter disorders--an overview.Journal of inherited metabolic disease · 2008Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
A 12-yr-old hypothyroid girl was diagnosed at birth as athyreotic because her thyroid gland could not be visualized by isotope scanning. Goiter development due to incomplete thyrotropin suppression, a thyroidal radioiodide uptake of < 1%, and a low saliva to plasma ratio of 2.5 suggested iodide (I-) transport defect. mRNA isolated from her thyroid gland and injected into Xenopus oocytes failed to increase I- transport. Sequencing of the entire Na+/I- symporter (NIS) cDNA revealed a C to G transversion of nucleotide (nt) 1146 in exon 6, resulting in a Gln 267 (CAG) to Glu (GAG) substitution. This missense mutation produces an NIS with undetectable I- transport activity when expressed in COS-7 cells. Although only this missense mutation was identified in thyroid and lymphocyte cDNA, genotyping revealed that the proposita and her unaffected brother and father were heterozygous for this mutation. However, amplification of cDNA with a primer specific for the wild-type nt 1146 yielded a sequence lacking 67 nt. Genomic DNA showed a C to G transversion of nt 1940, producing a stop codon as well as a new downstream cryptic 3' splice acceptor site in exon 13, responsible for the 67 nt deletion, frameshift, and premature stop predicting an NIS lacking 129 carboxy-terminal amino acids. This mutation was inherited from the mother and present in the unaffected sister. Thus, although the proposita is a compound heterozygote, because of the very low expression (< 2.5%) of one mutant allele, she is functionally hemizygous for an NIS without detectable bioactivity.
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