| Texto completo | |
| Autor(es): |
NOGUEIRA‚ C.R.
;
KOPP‚ P.
;
ARSEVEN‚ O.K.
;
SANTOS‚ C.L.S.
;
JAMESON‚ J.L.
;
MEDEIROS-NETO‚ G.
Número total de Autores: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | THYROID; v. 9, n. 11, p. 1063-1068, 1999. |
| Resumo | |
Constitutively activating mutations in the thyrotropin (TSH) receptor have been identified as a major molecular cause of hyperfunctioning thyroid adenomas. A smaller subset of these benign tumors is caused by constitutive activation of the adenylyl cyclase cascade by somatic mutations in the Gs alpha gene. In this study, we analyzed hyperfunctioning thyroid adenomas from seven Brazilian patients for TSH receptor and G(s alpha) gene mutations. Solitary autonomous thyroid adenomas were identified by ultrasound and scintigraphy, and DNA was extracted from adenomatous and periadenomatous tissue. Exons 9 and 10 of the TSH receptor gene, and exons 8 and 9 of the Gs alpha gene, were amplified by polymerase chain reaction (PCR) and subjected to direct sequence analysis. Six of seven adenomas harbored heterozygous mutations known to confer constitutive activity to the TSH receptor. In one case, aspartate 619 was substituted by glycine (D619G). In four adenomas, alanine 623 was replaced by valine (A623V). Both residues are located in the third intracellular loop. In one instance, aspartate 633 located in the sixth transmembrane domain was replaced by tyrosine (D633Y). In this patient, one allele also contained a change of aspartate 727 to glutamate (D727E). This substitution is thought to be a polymorphic variant of the wild-type but it has also been associated with toxic multinodular goiters. Functional comparison of D727 with E727 did not reveal differences in basal or TSH-stimulated cyclic adenosine monophosphate (cAMP)-dependent luciferase activity in transiently transfected cells. These results demonstrate a high prevalence of activating TSH receptor mutations in toxic adenomas in this small series from Brazil (similar to 86%). These findings are in agreement with reports from other countries with a marginal iodine intake but contrast with studies from regions with a high iodine intake where these mutations appear to be less prevalent. (AU) | |
| Processo FAPESP: | 96/00998-4 - Genética molecular de moléstias familiares e hereditárias dos sistemas endócrino e neuroendócrino |
| Beneficiário: | Geraldo Antônio de Medeiros Neto |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |