Evidence map›Paper›PMID 26204134›Full record

ArticleThe Journal of clinical endocrinology and metabolism2015

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

Open access · bronzeAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
5.2field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Silent but Not Harmless: A SynonymousFrontiers in endocrinology · 2022
    Article
  6. The Iodide Transport Defect-Causing Y348D Mutation in the NaThyroid : official journal of the American Thyroid Association · 2021
    Article
  7. Article
  8. Novel Compound Heterozygous Pathogenic Mutations ofFrontiers in endocrinology · 2021
    Article
  9. Review
  10. Implications of NaJournal of the Endocrine Society · 2019
    Review
  11. Article
  12. Review
  13. Na+ coordination at the Na2 site of the Na+/I- symporter.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 1 country.

Juan Pablo NicolaDepartment of Cellular and Molecular Physiology (J.P.N., A.R.-N., N.C.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Pediatrics (P.S., J.D.G.G.), Winthrop-University Hospital, Mineola, New York 11501; Department of Genetics (D.F.R.-B.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Department of Pediatrics (R.M.), Albert Einstein College of Medicine, Bronx, New York 10467; and Department of Biophysics and Biophysical Chemistry (L.M.A.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Andrea Reyna-NeyraDepartment of Cellular and Molecular Physiology (J.P.N., A.R.-N., N.C.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Pediatrics (P.S., J.D.G.G.), Winthrop-University Hospital, Mineola, New York 11501; Department of Genetics (D.F.R.-B.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Department of Pediatrics (R.M.), Albert Einstein College of Medicine, Bronx, New York 10467; and Department of Biophysics and Biophysical Chemistry (L.M.A.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Paul SaengerDepartment of Cellular and Molecular Physiology (J.P.N., A.R.-N., N.C.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Pediatrics (P.S., J.D.G.G.), Winthrop-University Hospital, Mineola, New York 11501; Department of Genetics (D.F.R.-B.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Department of Pediatrics (R.M.), Albert Einstein College of Medicine, Bronx, New York 10467; and Department of Biophysics and Biophysical Chemistry (L.M.A.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
David F Rodriguez-BuriticaDepartment of Cellular and Molecular Physiology (J.P.N., A.R.-N., N.C.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Pediatrics (P.S., J.D.G.G.), Winthrop-University Hospital, Mineola, New York 11501; Department of Genetics (D.F.R.-B.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Department of Pediatrics (R.M.), Albert Einstein College of Medicine, Bronx, New York 10467; and Department of Biophysics and Biophysical Chemistry (L.M.A.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
José David Gamez GodoyDepartment of Cellular and Molecular Physiology (J.P.N., A.R.-N., N.C.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Pediatrics (P.S., J.D.G.G.), Winthrop-University Hospital, Mineola, New York 11501; Department of Genetics (D.F.R.-B.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Department of Pediatrics (R.M.), Albert Einstein College of Medicine, Bronx, New York 10467; and Department of Biophysics and Biophysical Chemistry (L.M.A.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Radhika MuzumdarDepartment of Cellular and Molecular Physiology (J.P.N., A.R.-N., N.C.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Pediatrics (P.S., J.D.G.G.), Winthrop-University Hospital, Mineola, New York 11501; Department of Genetics (D.F.R.-B.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Department of Pediatrics (R.M.), Albert Einstein College of Medicine, Bronx, New York 10467; and Department of Biophysics and Biophysical Chemistry (L.M.A.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
L Mario AmzelDepartment of Cellular and Molecular Physiology (J.P.N., A.R.-N., N.C.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Pediatrics (P.S., J.D.G.G.), Winthrop-University Hospital, Mineola, New York 11501; Department of Genetics (D.F.R.-B.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Department of Pediatrics (R.M.), Albert Einstein College of Medicine, Bronx, New York 10467; and Department of Biophysics and Biophysical Chemistry (L.M.A.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Nancy CarrascoDepartment of Cellular and Molecular Physiology (J.P.N., A.R.-N., N.C.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Pediatrics (P.S., J.D.G.G.), Winthrop-University Hospital, Mineola, New York 11501; Department of Genetics (D.F.R.-B.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Department of Pediatrics (R.M.), Albert Einstein College of Medicine, Bronx, New York 10467; and Department of Biophysics and Biophysical Chemistry (L.M.A.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Yale University · USWinthrop-University Hospital · USJohns Hopkins Medicine · USUniversity of Alabama at Birmingham · USYeshiva University · US

Funding

THYROID SODIUM I/ SYMPORTERR01DK041544 · NIDDK · YESHIVA UNIVERSITY · PI ABBOTT, GEOFFREY W, CARRASCO, NANCY · 1989 to 2017
$5.6M
Mechanism of I- transport by the Na+/l- symporter (NIS)R01GM114250 · NIGMS · YALE UNIVERSITY · PI Nancy Carrasco · 2016 to 2026
$4.8M
NIDDK NIH HHS DK-41544NIDDK NIH HHS R01 DK041544NIGMS NIH HHS R01 GM114250
6 · The paper itself

Abstract

contextIodide (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.

objectiveThis study aimed to determine the basis of a patient's ITD clinical phenotype, by sequencing her slc5a5 gene.

designGenomic 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.

resultsWe 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.

conclusionsA nonpolar residue at position 270, which all members of the SLC5A family have, is required for NIS plasma membrane targeting.

Indexed as

MutationAllelesChildCognition DisordersCongenital HypothyroidismDNA Mutational AnalysisFemaleGrowth DisordersHumansPhenotypeSodium-Iodide SymportersSymportersSodium-Iodide SymportersSymporters

Identifiers

PMID26204134
PMCPMC4596044
OpenAlexW1869582472

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.