| Texto completo | |
| Autor(es): |
Siviero-Miachon, Adriana A.
;
Kizys, Marina M. L.
;
Ribeiro, Manuela M.
;
Garcia, Fabiola Esgrignoli
;
Spinola-Castro, Angela M.
;
Dias da Silva, Magnus R.
Número total de Autores: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | ENDOCRINE RESEARCH; v. 42, n. 2, p. 117-124, 2017. |
| Citações Web of Science: | 3 |
| Resumo | |
Purpose: Testotoxicosis is an autosomal dominant form of gonadotropin-independent precocious puberty caused by heterozygous constitutively activating mutations of the luteinizing hormone/choriogonadotropin receptor (LHCGR) gene. The aim of this study was to describe two Brazilian siblings with testotoxicosis, to confirm the molecular diagnosis, and to perform an in silico analysis of a novel mutation in the hot spot of the LHCGR gene. Materials and methods: Molecular analysis of the mutation on the LHCGR gene was performed by direct Sanger sequencing, followed by an in silico analysis using HOPE bioinformatics tool to predict a functional defect of the mutant. Results: Both patients presented with gonadotropin-independent precocious puberty before the age of four years. Genetic analysis revealed a novel non-maternally inherited p.Asp578Val mutation of the LHCGR gene. An in silico analysis showed that the p.Asp578Val mutation disturbed amino acid physicochemical features regarding its size, charge, and hydrophobicity value. Conclusions: Clinical and hormonal profile of the siblings here evaluated was not different while compared to those patients previously described. An in silico mutation analysis reinforced the causative role of recurrent activating mutations in the intracellular loop and transmembrane helices of the LHCGR. The segregation of this mutation with the offsprings' phenotype indicated that it is causative. (AU) | |
| Processo FAPESP: | 06/60402-1 - Carcinoma medular da tiróide: revisitação à clínica, à biologia molecular, à bioquímica e à biologia do desenvolvimento depois dos achados da genética molecular |
| Beneficiário: | Rui Monteiro de Barros Maciel |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 11/20747-8 - Investigação clínica, bioquímica e molecular da paralisia periódica tirotóxica |
| Beneficiário: | Magnus Régios Dias da Silva |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 14/15948-2 - Hipotiroidismo congênito: validação funcional in vivo do novo gene-candidato CCDC para o desenvolvimento da hemiagenesia tiroidiana |
| Beneficiário: | Marina Malta Letro Kizys Polisel |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto |
| Processo FAPESP: | 12/01628-0 - Disgenesias tiroidianas: análise molecular e estudo funcional de mutações em genes candidatos a partir do sequenciamento de última geração numa coorte de 268 casos |
| Beneficiário: | Marina Malta Letro Kizys Polisel |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |