Sodium/iodide symporter mutant V270E causes stunted growth but no cognitive deficiency

Juan Pablo Nicola, Andrea Reyna-Neyra, Paul Saenger, David F. Rodriguez-Buritica, José David Gamez Godoy, Radhika Muzumdar, L. Mario Amzel, Nancy Carrasco

Research output: Contribution to journalArticlepeer-review


Context: Iodide (I-), an essential constituent of the thyroid hormones, is actively accumulated in the thyroid by the Na+/I- symporter (NIS), a key plasma membrane protein encoded by the slc5a5 gene. Mutations in slc5a5 cause I- transport defects (ITDs), autosomal-recessive disorders in which I- accumulation is totally or partially impaired, leading to congenital hypothyroidism. The characterization of NIS mutants has yielded significant insights into the molecular mechanism of NIS. Objective: This study aimed to determine the basis of a patient's ITD clinical phenotype, by sequencing her slc5a5 gene. Design: Genomic DNA was purified and the slc5a5 gene sequence determined. Functional in vitro studies were performed to characterize the V270E NIS mutant. Patient: The index patient was diagnosed with hypothyroidism with minimal radioiodide uptake in a normally located, although enlarged, thyroid gland. Results: We identified a new NIS mutation: V270E. The patient had the compound heterozygous NIS mutation R124H/V270E. R124H NIS has been characterized previously. We show that V270E markedly reduces I- uptake via a pronounced (but not total) impairment of the protein's plasma membrane targeting. Remarkably, V270E is intrinsically active. Therefore, a negative charge at position 270 interferes with NIS cell surface trafficking. The patient's minimal I- uptake enabled sufficient thyroid hormone biosynthesis to prevent cognitive impairment. Conclusions: A nonpolar residue at position 270, which all members of the SLC5A family have, is required for NIS plasma membrane targeting.

Original languageEnglish (US)
Pages (from-to)E1353-E1361
JournalJournal of Clinical Endocrinology and Metabolism
Issue number10
StatePublished - Oct 1 2015

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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