title: Congenital hypothyroidism with goiter in toy fox terriers.
abstract: Congenital hypothyroidism with goiter was observed to segregate as a simple autosomal recessive trait in Toy Fox Terriers (TFTs). Neonatal affected pups exhibited inactivity, abnormal hair coat, stenotic ear canals, and delayed eye opening. Palpable ventrolateral cervical swellings were evident by 1 week of age. Serum thyroid hormone and thyroid-stimulating hormone concentrations were low and high, respectively. Histologic examination of the cervical masses disclosed cuboidal to columnar follicular epithelial cell hyperplasia with widely varying follicular size, shape, and amount of colloid. Oral thyroid hormone replacement therapy restored near-normal growth and development. At 8 weeks of age, radioiodine uptake and perchlorate discharge testing indicated an iodine organification defect. Biochemical analysis of thyroid tissue from affected dogs demonstrated enzymatic iodine oxidation deficiency and lack of sodium dodecyl sulfate-resistant thyroglobulin dimers, suggesting thyroid peroxidase deficiency. A nonsense mutation in the thyroid peroxidase gene of affected dogs was discovered and demonstrated to segregate with the disease. A DNA-based carrier test was developed and currently is used by TFT breeders to prevent this disorder.
authors.affiliation: Laboratory of Comparative Medical Genetics, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA. fyfe@cvm.msu.edu
authors.forename: John C
authors.initials: JC
authors.lastname: Fyfe
authors.forename: Kit
authors.initials: K
authors.lastname: Kampschmidt
authors.forename: Van
authors.initials: V
authors.lastname: Dang
authors.forename: Brian A
authors.initials: BA
authors.lastname: Poteet
authors.forename: Qianchuan
authors.initials: Q
authors.lastname: He
authors.forename: Charles
authors.initials: C
authors.lastname: Lowrie
authors.forename: Peter A
authors.initials: PA
authors.lastname: Graham
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Fetro
mesh_terms: D000818:Animals; D018389:Codon, Nonsense / Q000235:genetics; D003409:Congenital Hypothyroidism; D004252:DNA Mutational Analysis; D004283:Dog Diseases / Q000151:congenital* / Q000235:genetics*; D004285:Dogs; D005260:Female; D006042:Goiter / Q000150:complications / Q000235:genetics* / Q000662:veterinary*; D006579:Heterozygote; D007037:Hypothyroidism / Q000150:complications / Q000235:genetics* / Q000662:veterinary*; D007453:Iodide Peroxidase / Q000235:genetics; D008297:Male; D010375:Pedigree
chemical_list: D018389:Codon, Nonsense; D007453:Iodide Peroxidase