This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kosugi, S. Articles by Dean, H. J. Search for Related Content PubMed PubMed Citation Articles by Kosugi, S. Articles by Dean, H. J.

A Novel Mutation in the Sodium/Iodide Symporter Gene in the Largest Family with Iodide Transport Defect¹

Department of Laboratory Medicine and Clinical Genetics Unit (S.K.), Kyoto 606-8507 Japan; and the Department of Pediatrics, University of Manitoba (S.B., H.J.D.), Winnipeg, Manitoba, Canada R3A 1R9

Address all correspondence and requests for reprints to: Dr. Shinji Kosugi, Department of Laboratory Medicine, Kyoto University School of Medicine, 54 Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: kosugi{at}kuhp.kyoto-u.ac.jp

We previously reported nine children with an autosomally recessive form of congenital hypothyroidism due to an iodide transport defect in a large Hutterite family with extensive consanguinity living in central Canada. Since the original report, we have diagnosed congenital hypothyroidism by newborn TSH screening in 9 additional children from the family. We performed direct sequencing of the PCR products of each NIS (sodium/iodide symporter) gene exon with flanking introns amplified from genomic DNA extracted from peripheral blood cells of the patients. We identified a novel NIS gene mutation, G395R (Gly³⁹⁵Arg; GGAAGA), in 10 patients examined in the present study. All of the parents tested were heterozygous for the mutation, suggesting that the patients were homozygous. The mutation was located in the 10th transmembrane helix. Expression experiments by transfection of the mutant NIS complimentary DNA into COS-7 cells showed no perchlorate-sensitive iodide uptake, confirming that the mutation is the direct cause of the iodide transport defect in these patients. A patient who showed an intermediate saliva/serum technetium ratio (14.0; normal, 20) and was considered to have a partial or less severe defect in the previous report (IX-24) did not have a NIS gene mutation. It is now possible to use gene diagnostics of this unique NIS mutation to identify patients with congenital hypothyroidism due to an iodide transport defect in this family and to determine the carrier state of potential parents for genetic counseling and arranging rapid and early diagnosis of their infants.

This article has been cited by other articles:

				M. D. Reed-Tsur, A. De la Vieja, C. S. Ginter, and N. Carrasco Molecular Characterization of V59E NIS, a Na+/I- Symporter Mutant that Causes Congenital I- Transport Defect Endocrinology, June 1, 2008; 149(6): 3077 - 3084. [Abstract] [Full Text] [PDF]

				G. Riesco-Eizaguirre and P. Santisteban A perspective view of sodium iodide symporter research and its clinical implications. Eur. J. Endocrinol., October 1, 2006; 155(4): 495 - 512. [Abstract] [Full Text] [PDF]

				G. Szinnai, S. Kosugi, C. Derrien, N. Lucidarme, V. David, P. Czernichow, and M. Polak Extending the Clinical Heterogeneity of Iodide Transport Defect (ITD): A Novel Mutation R124H of the Sodium/Iodide Symporter Gene and Review of Genotype-Phenotype Correlations in ITD J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1199 - 1204. [Abstract] [Full Text] [PDF]

				A. De la Vieja, C. S. Ginter, and N. Carrasco Molecular Analysis of a Congenital Iodide Transport Defect: G543E Impairs Maturation and Trafficking of the Na+/I- Symporter Mol. Endocrinol., November 1, 2005; 19(11): 2847 - 2858. [Abstract] [Full Text] [PDF]

				K. Krohn, D. Fuhrer, Y. Bayer, M. Eszlinger, V. Brauer, S. Neumann, and R. Paschke Molecular Pathogenesis of Euthyroid and Toxic Multinodular Goiter Endocr. Rev., June 1, 2005; 26(4): 504 - 524. [Abstract] [Full Text] [PDF]

				A. De la Vieja, C. S. Ginter, and N. Carrasco The Q267E mutation in the sodium/iodide symporter (NIS) causes congenital iodide transport defect (ITD) by decreasing the NIS turnover number J. Cell Sci., February 15, 2004; 117(5): 677 - 687. [Abstract] [Full Text] [PDF]

				P. Caron, C. M. Moya, D. Malet, V. J. Gutnisky, B. Chabardes, C. M. Rivolta, and H. M. Targovnik Compound Heterozygous Mutations in the Thyroglobulin Gene (1143delC and 6725G->A [R2223H]) Resulting in Fetal Goitrous Hypothyroidism J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3546 - 3553. [Abstract] [Full Text] [PDF]

				S. Selmi-Ruby, C. Watrin, S. Trouttet-Masson, F. Bernier-Valentin, V. Flachon, Y. Munari-Silem, and B. Rousset The Porcine Sodium/Iodide Symporter Gene Exhibits an Uncommon Expression Pattern Related to the Use of Alternative Splice Sites not Present in the Human or Murine Species Endocrinology, March 1, 2003; 144(3): 1074 - 1085. [Abstract] [Full Text] [PDF]

				O. Dohan, A. De la Vieja, V. Paroder, C. Riedel, M. Artani, M. Reed, C. S. Ginter, and N. Carrasco The Sodium/Iodide Symporter (NIS): Characterization, Regulation, and Medical Significance Endocr. Rev., February 1, 2003; 24(1): 48 - 77. [Abstract] [Full Text] [PDF]

				S. Kosugi, H. Okamoto, A. Tamada, and F. Sanchez-Franco A Novel Peculiar Mutation in the Sodium/Iodide Symporter Gene in Spanish Siblings with Iodide Transport Defect J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3830 - 3836. [Abstract] [Full Text] [PDF]

				O. Dohan, M. V. Gavrielides, C. Ginter, L. M. Amzel, and N. Carrasco Na+/I- Symporter Activity Requires a Small and Uncharged Amino Acid Residue at Position 395 Mol. Endocrinol., August 1, 2002; 16(8): 1893 - 1902. [Abstract] [Full Text] [PDF]

				S. M. Jhiang A Monoclonal Antibody Recognizing the Extracellular Domain of Human Na+/I- Symporter and Its Potential Applications J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2364 - 2365. [Full Text]

				J. Pohlenz, L. Duprez, R. E. Weiss, G. Vassart, S. Refetoff, and S. Costagliola Failure of Membrane Targeting Causes the Functional Defect of Two Mutant Sodium Iodide Symporters J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2366 - 2369. [Abstract] [Full Text]