title: Mutations of the thyroglobulin gene and its relevance to thyroid disorders.
abstract: OBJECTIVE
  To perform an update review on thyroglobulin gene mutations associated with congenital hypothyroidism, thyroid cancer, and autoimmunity.
  
  
  RESULTS
  Forty-two thyroglobulin mutations have been identified in dyshormonogenetic congenital hypothyroidism. Clinical and laboratory criteria defining defective thyroglobulin synthesis are mostly related to thyroglobulin mutations, generally caused by intracellular thyroglobulin transport defects to the colloid rather than defects in thyroid hormones synthesis. Some mutated thyroglobulin may escape the rigorous chaperone control and reach the colloid, allowing a wide phenotypic spectrum that includes euthyroidism in an adequate iodine environment. In some patients, continuous levothyroxine treatment does not reduce elevated serum thyroid-stimulating hormone (TSH) levels that may lead to goiter development. Prenatally, inactive mutant thyroglobulin will not be able to synthesize thyroid hormones and may increase pituitary thyrotroph threshold for thyroid hormone feedback. Congenital goiter is a risk factor for thyroid cancer and some thyroglobulin variants may confer susceptibility to thyroid autoimmunity.
  
  
  CONCLUSIONS
  Advances in the understanding of thyroglobulin genetic defects and its severity should allow researchers to perform adequate molecular diagnosis, genetic counseling, and intrauterine treatment to prevent subtle deficits in central nervous system development. This knowledge should improve the understanding of physiological functions of the thyroid and influence of nutritional iodine.
authors.affiliation: Thyroid Study Unit (LIM-25), Division of Endocrinology, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Ileana G S
authors.initials: IG
authors.lastname: Rubio
authors.forename: Geraldo
authors.initials: G
authors.lastname: Medeiros-Neto
mesh_terms: D019281:Dimerization; D005315:Fetal Diseases / Q000235:genetics; D005838:Genotype; D006801:Humans; D009154:Mutation / Q000502:physiology*; D010641:Phenotype; D021381:Protein Transport; D013954:Thyroglobulin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D013959:Thyroid Diseases / Q000235:genetics*; D013961:Thyroid Gland / Q000378:metabolism
chemical_list: D013954:Thyroglobulin