title: Congenital hypothyroidism and late-onset goiter: identification and characterization of a novel mutation in the sodium/iodide symporter of the proband and family members.
abstract: BACKGROUND
  Iodide transport defects (ITDs), rare causes of congenital hypothyroidism (CH), have been shown to arise from abnormalities of the sodium/iodide symporter (NIS). We describe a 16-year-old girl with CH caused by an ITD resulting from a novel mutation of NIS.
  
  
  CONCLUSIONS
  A 16-year-old girl with CH diagnosed by a neonatal screening program received early treatment with L-thyroxine replacement therapy. A (123)I scan had failed to reveal any iodide uptake by the thyroid and salivary glands; thus, thyroid agenesis was diagnosed. Thyroglobulin (Tg) was not measured when she was a neonate or infant. Unexpectedly, at the age of 14.5 years, a nodular goiter and high serum Tg concentrations (303 ng/mL; normal, <50) were identified. Her thyroid radioactive iodine uptake was very low as was the saliva to plasma iodide ratio (0.5). Analysis of her NIS gene revealed an in-frame six-nucleotide deletion of the coding sequence (1206-1211delGTCGGC) corresponding to the deletion of amino acids 287 and 288 of the human NIS protein located at the beginning of the VIII transmembrane segment. The proband was homozygous for this deletion, whereas both unrelated parents and her brother were heterozygous. COS-7 cells transfected with the mutant NIS failed to concentrate iodide, confirming that the mutation was the direct cause of the ITD in this patient.
  
  
  CONCLUSIONS
  We describe a patient with CH caused by a previously not described mutation of the NIS gene that was inherited from her parents. We therefore recommend that thyroid ultrasonography be performed in CH patients with low radioactive iodine uptake and elevated serum Tg.
authors.affiliation: Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Montanelli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agretti
authors.forename: Giuseppina de
authors.initials: Gd
authors.lastname: Marco
authors.forename: Brunella
authors.initials: B
authors.lastname: Bagattini
authors.forename: Claudia
authors.initials: C
authors.lastname: Ceccarelli
authors.forename: Federica
authors.initials: F
authors.lastname: Brozzi
authors.forename: Teresa
authors.initials: T
authors.lastname: Lettiero
authors.forename: Manuela
authors.initials: M
authors.lastname: Cerbone
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Mariacarolina
authors.initials: M
authors.lastname: Salerno
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Massimo
authors.initials: M
authors.lastname: Tonacchera
mesh_terms: D000293:Adolescent; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D003409:Congenital Hypothyroidism / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006042:Goiter / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D015997:Neonatal Screening; D010375:Pedigree; D027981:Symporters / Q000235:genetics*; D013954:Thyroglobulin / Q000097:blood; D013961:Thyroid Gland / Q000002:abnormalities; D000099209:Sodium-Iodide Symporters
chemical_list: D027981:Symporters; D013954:Thyroglobulin; D000099209:Sodium-Iodide Symporters