| Texto completo | |
| Autor(es): |
Crespo, Raiane P.
;
Rocha, Thais P.
;
Montenegro, Luciana R.
;
Nishi, Mirian Y.
;
Jorge, Alexander A. L.
;
Maciel, Gustavo A. R.
;
Baracat, Edmund
;
Latronico, Ana Claudia
;
Mendonca, Berenice B.
;
Gomes, Larissa G.
Número total de Autores: 10
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF THE ENDOCRINE SOCIETY; v. 6, n. 9, p. 10-pg., 2022-09-01. |
| Resumo | |
Context: Polycystic ovary syndrome (PCOS) etiology remains to be elucidated, but familial clustering and twin studies have shown a strong heritable component. Objective: The purpose of this study was to identify rare genetic variants that are associated with the etiology of PCOS in a preselected cohort. Methods: This prospective study was conducted among a selected group of women with PCOS. The study's inclusion criteria were patients with PCOS diagnosed by the Rotterdam criteria with the following phenotypes: severe insulin resistance (IR), normoandrogenic-normometabolic phenotype, adrenal hyperandrogenism, primary amenorrhea, and familial PCOS. Forty-five patients were studied by target sequencing, while 8 familial cases were studied by whole exome sequencing. Results: Patients were grouped according to the inclusion criteria with the following distribution: 22 (41.5%) with severe IR, 13 (24.5%) with adrenal hyperandrogenism, 7 (13.2%) with normoandrogenic phenotype, 3 (5.7%) with primary amenorrhea, and 8 (15.1%) familial cases. DNA sequencing analysis identified 1 pathogenic variant in LMNA, 3 likely pathogenic variants in INSR, PIK3R1, and DLK1, and 6 variants of uncertain significance level with interesting biologic rationale in 5 genes (LMNA, GATA4, NR5A1, BMP15, and FSHR). LMNA was the most prevalent affected gene in this cohort (3 variants). Conclusion: Several rare variants in genes related to IR were identified in women with PCOS. Although IR is a common feature of PCOS, patients with extreme or atypical phenotype should be carefully evaluated to rule out monogenic conditions. (AU) | |
| Processo FAPESP: | 15/17350-0 - Identificação de Genes Associados à Etiologia da Síndrome dos Ovários Policísticos por Sequenciamento em Larga Escala |
| Beneficiário: | Larissa Garcia Gomes |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 19/27631-7 - Estudos genéticos e epigenéticos dos distúrbios endócrinos do eixo reprodutivo |
| Beneficiário: | Ana Claudia Latronico Xavier |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |