Mutations of the thyroglobulin gene and its relevance to thyroid disorders

Autor(es)

Rubio, Ileana G. S. ^[1] ; Medeiros-Neto, Geraldo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Thyroid Study Unit LIM 25, Div Endocrinol, BR-01246903 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY; v. 16, n. 5, p. 373-378, OCT 2009.
• Citações Web of Science: 15

Resumo

Purpose of review To perform an update review on thyroglobulin gene mutations associated with congenital hypothyroidism, thyroid cancer, and autoimmunity. Recent findings 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. Summary 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. (AU)

• Processo FAPESP: 03/02989-8 - Hipotireoidismo congênito por deficiência na síntese de tireoglobulina: rastreamento e estudo funcional de mutações do gene da tireoglobulina
• Beneficiário: Viviane Lyrio Do Valle de Pardo Blois
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto