title: A novel peculiar mutation in the sodium/iodide symporter gene in spanish siblings with iodide transport defect.
abstract: Previously, we reported two Spanish siblings with congenital hypothyroidism due to total failure of iodide transport. These were the only cases reported to date who received long-term iodide treatment over 10 yr. We examined the sodium/iodide symporter (NIS) gene of these patients. A large deletion was observed by long and accurate PCR using primers derived from introns 2 and 7 of the NIS gene. PCR-direct sequencing revealed a deletion of 6192 bases spanning from exon 3 to intron 7 and an inverted insertion of a 431-base fragment spanning from exon 5 to intron 5 of the NIS gene. The patients were homozygous for the mutation, and their mother was heterozygous. In the mutant, deletion of exons 3-7 was suggested by analysis using programs to predict exon/intron organization, resulting in an in-frame 182-amino acid deletion from Met(142) in the fourth transmembrane domain to Gln(323) in the fourth exoplasmic loop. The mutant showed no iodide uptake activity when transfected into COS-7 cells, confirming that the mutation was the direct cause of the iodide transport defect in these patients. Further, the mutant NIS protein was synthesized, but not properly expressed, on the cell surface, but was mostly accumulated in the cytoplasm, suggesting impaired targeting to the plasma membrane.
authors.affiliation: Department of Clinical Genetics, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan. kosugi@kuhp.kyoto-u.ac.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Kosugi
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Aiko
authors.initials: A
authors.lastname: Tamada
authors.forename: F
authors.initials: F
authors.lastname: Sanchez-Franco
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D005091:Exons; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns; D007454:Iodides / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009679:Nuclear Family; D010375:Pedigree; D010641:Phenotype; D017434:Protein Structure, Tertiary; D013030:Spain; D027981:Symporters / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000099209:Sodium-Iodide Symporters
chemical_list: D007454:Iodides; D027981:Symporters; D000099209:Sodium-Iodide Symporters