title: [Molecular biology of the genetic defects of synthesis, transport and peripheral action of the thyroid gland hormones].
abstract: Recent advances in molecular biology and the use of modern techniques made possible the identification and cloning of DNA portions of the human genome encoding proteins that are important for the synthesis, storage, transport and action of thyroid hormones. These achievements have led to the diagnosis of the basic defects at the DNA level and the understanding of the biochemical disturbance in the genetic disorders of thyroid metabolism. In patients with defective expression of thyroid peroxidase (TPO) the presence of polymorphism (RFLP) associated with Bgl-I segregates with the affected individual with goiter, hypothyroidism and positive perchlorate discharge test. Defects in the thyroglobulin are either quantitative (no Tg is synthetized) or qualitative (an abnormal Tg is expressed). Low messenger RNA codifying for Tg was present in one of the families with virtual absence of Tg in serum and thyroid tissue. In another family absence of sialic acid incorporation into the Tg molecule produced a Tg with structural defect, incapable of T3 and T4 generation. A point mutation in the nucleotide 281 of exon 5 has been claimed as the mutation producing a defective TBG. Finally, the resistance to thyroid hormone action is linked to a mutation in the c-erb-A beta, detected by the presence of a polymorphism EcoRV, that will encode a defective protein or will produce a protein that might block the T3 binding to the receptor.
authors: Unidade de Tireóide, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo.
authors: G
authors: G
authors: Medeiros-Neto
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D004274:DNA, Recombinant; D004351:Drug Resistance; D015698:Genomic Library; D006801:Humans; D007037:Hypothyroidism / Q000201:enzymology / Q000235:genetics; D007453:Iodide Peroxidase / Q000172:deficiency; D010375:Pedigree; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D013954:Thyroglobulin / Q000172:deficiency; D013963:Thyroid Hormones / Q000172:deficiency*; D013975:Thyroxine-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004274:DNA, Recombinant; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D013975:Thyroxine-Binding Proteins; D013954:Thyroglobulin; D007453:Iodide Peroxidase
vernacular_title: Biologia molecular dos defeitos genéticos de síntese, transporte e ação periférica dos hormônios da glândula tireóide.