title: [The thyroid as a model for molecular mechanisms in genetic diseases].
abstract: Thyroid diseases constitute a heterogeneous collection of abnormalities associated with mutations in genes responsible for the development of thyroid: thyroid transcription factor-1 (TTF-1), thyroid transcriptions factor-2 (TTF-2) and PAX8, or in one of the genes coding for the proteins involved in thyroid hormone biosynthesis such as thyroglobulin (TG), thyroperoxidase (TPO), hydrogen peroxide-generating system (DUOX2), sodium/iodide symporter (NIS), pendrin (PDS), TSH and TSH receptor (TSHr). Congenital hypothyroidism occurs with a prevalence of 1 in 4000 newborns. Patients with this syndrome can be divided into two groups: nongoitrous (dysem/bryogenesis) or goitrous (dyshormonogenesis) congenital hypothyroidism. The dysembryogenesis group, which accounts for 85% of the cases, results from ectopy, agenesis and hypoplasia. In a minority of these patients, the congenital hypothyroidism is associated with mutations in TTF-1, TTF-2, PAX-8, TSH or TSHr genes. The presence of congenital goiter (15% of the cases) has been linked to mutations in the NIS, TG, TPO, DUOX2 or PDS genes. The congenital hypothyroidism with dyshormonogenesis is transmitted as an autosomal recessive trait. Somatic mutations of the TSHr have been identified in hyperfunctioning thyroid adenomas. Another established thyroid disease is the resistance to thyroid hormone (RTH). It is a syndrome of reduced tissue responsiveness to hormonal action caused by mutations located in the thyroid hormone receptor beta (TRbeta) gene. Mutant TRbetas interfere with the function of the wild-type receptor by a dominant negative mechanism. In conclusion, the identification of mutations in the thyroid expression genes has provided important insights into structure-function relationships. The thyroid constitutes an excellent model for the molecular study of genetic diseases.
authors.affiliation: Cátedra de Genética y Biología Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: Carina M
authors.initials: CM
authors.lastname: Rivolta
authors.forename: Christian M
authors.initials: CM
authors.lastname: Moya
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Esperante
authors.forename: Viviana J
authors.initials: VJ
authors.lastname: Gutnisky
authors.forename: Viviana
authors.initials: V
authors.lastname: Varela
authors.forename: Hector M
authors.initials: HM
authors.lastname: Targovnik
mesh_terms: D003409:Congenital Hypothyroidism / Q000235:genetics* / Q000378:metabolism; D006042:Goiter / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006980:Hyperthyroidism / Q000235:genetics* / Q000378:metabolism; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011989:Receptors, Thyrotropin / Q000235:genetics; D013963:Thyroid Hormones / Q000096:biosynthesis / Q000235:genetics
chemical_list: D011989:Receptors, Thyrotropin; D013963:Thyroid Hormones; D007453:Iodide Peroxidase