RAIANE PINA CRESPO TEIXEIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- High-throughput Sequencing to Identify Monogenic Etiologies in a Preselected Polycystic Ovary Syndrome Cohort(2022) 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.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.
- DLK1 Is a Novel Link Between Reproduction and Metabolism(2019) GAMES, Larissa G.; CUNHA-SILVA, Marina; CRESPO, Raiane P.; RAMOS, Carolina O.; MONTENEGRO, Luciana R.; CANTON, Ana; LEES, Melissa; SPOUDEAS, Helen; DAUBER, Andrew; MACEDO, Delanie B.; BESSA, Danielle S.; MACIEL, Gustavo A.; BARACAT, Edmund C.; JORGE, Alexander A. L.; MENDONCA, Berenice B.; BRITO, Vinicius N.; LATRONICO, Ana ClaudiaBackground: Delta-like homolog 1 (DLK1), also called preadipocyte factor 1, prevents adipocyte differentiation and has been considered a molecular gatekeeper of adipogenesis. A DLK1 complex genomic defect was identified in five women from a single family with central precocious puberty (CPP) and increased body fat percentage. Methods: We studied 60 female patients with a diagnosis of CPP or history of precocious menarche. Thirty-one of them reported a family history of precocious puberty. DLK1 DNA sequencing was performed in all patients. Serum DLK1 concentrations were measured using an ELISA assay in selected cases. Metabolic and reproductive profiles of adult women with CPP caused by DLK1 defects were compared with those of 20 women with idiopathic CPP. Results: We identified three frameshift mutations of DLK1 (p.Gly199Alafs*11, p.Va1271Cysfs*14, and p.Pro160Leufs*50) in five women from three families with CPP. Segregation analysis was consistent with the maternal imprinting of DLK1. Serum DLK1 concentrations were undetectable in three affected women. Metabolic abnormalities, such as overweight/obesity, early-onset glucose intolerance/type 2 diabetes mellitus, and hyperlipidemia, were more prevalent in women with the DLK1 mutation than in the idiopathic CPP group. Notably, the human metabolic alterations were similar to the previously described dlk1-null mice phenotype. Two sisters who carried the p.Gly199Alafs*11 mutation also exhibited polycystic ovary syndrome and infertility. Conclusions: Loss-of-function mutations of DLK1 are a definitive cause of familial CPP. The high prevalence of metabolic alterations in adult women who experienced CPP due to DLK1 defects suggests that this antiadipogenic factor represents a link between reproduction and metabolism.
- Persistent Poor Metabolic Profile in Postmenopausal Women With Ovarian Hyperandrogenism After Testosterone Level Normalization(2019) ROCHA, Thais; CRESPO, Raiane P.; YANCE, Viviane V. R.; HAYASHIDA, Sylvia A.; BARACAT, Edmund C.; CARVALHO, Filomena; DOMENICE, Sorahia; MENDONCA, Berenice B.; GOMES, Larissa G.Context: Data on prevalence of metabolic risk factors in hyperandrogenic postmenopausal women are limited. Also, the correlation between metabolic disorders and androgen excess in this scenario is poorly understood. Objectives: We aimed to assess the prevalence of obesity, hypertension, type 2 diabetes (T2D), and dyslipidemia (DLP) in postmenopausal women with hyperandrogenism of ovarian origin before and after surgical normalization of testosterone (T) levels, as well as the impact of androgen normalization on body mass index (BMI), glucose, and lipid metabolism. Design: Retrospective study. Setting: Tertiary health center. Participants: Twenty-four Brazilian women with postmenopausal hyperandrogenism who underwent bilateral oophorectomy between 2004 and 2014 and had histologically confirmed virilizing ovarian tumor (VOT) or ovarian hyperthecosis (OH) and T-level normalization after surgery were selected. Main Outcome Measures: FSH, LH, total and calculated free T, BMI, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) serum levels were accessed before (n = 24) and 24 months after (n 5 19) bilateral oophorectomy. Results: At baseline, the overall prevalence rates of obesity, T2D, DLP, and hypertension were 58.3%, 83.3%, 66.7%, and 87.5%, respectively. No significant difference in prevalence was found between patients with OH and VOTs. At follow-up, FSH, LH, and total and free T levels had returned to menopausal physiologic levels, but mean BMI and mean FPG, HbA1c, LDL-C, HDL-C, and TG levels did not differ from baseline. Conclusions: Postmenopausal hyperandrogenism is associated with adverse metabolic risk. Longterm normalization of testosterone levels did not improve BMI, glucose, or lipid metabolism.
- An update of genetic basis of PCOS pathogenesis(2018) CRESPO, Raiane P.; BACHEGA, Tania A. S. S.; MENDONCA, Berenice B.; GOMES, Larissa G.Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder that affects 5-20% of reproductive age women. PCOS clinical symptoms include hirsutism, menstrual dysfunction, infertility, obesity and metabolic syndrome. There is a wide heterogeneity in clinical manifestations and metabolic complications. The pathogenesis of PCOS is not fully elucidated, but four aspects seem to contribute to the syndrome to different degrees: increased ovarian and/or adrenal androgen secretion, partial folliculogenesis arrest, insulin resistance and neuroendocrine axis dysfunction. A definitive etiology remains to be elucidated, but PCOS has a strong heritable component indicated by familial clustering and twin studies. Genome Wide Association Studies (GWAS) have identified several new risk loci and candidate genes for PCOS. Despite these findings, the association studies have explained less than 10% of heritability. Therefore, we could speculate that different phenotypes and subphenotypes are caused by rare private genetic variants. Modern genetic studies, such as whole exome and genome sequencing, will help to clarify the contribution of these rare genetic variants on different PCOS phenotypes.