ANA CLAUDIA LATRONICO XAVIER
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
40 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 40
- Genotype-Phenotype Correlations in Central Precocious Puberty Caused by MKRN3 Mutations (vol 106, pg 1041, 2021)(2021) SERAPHIM, C. E.; CANTON, A. P. M.; MONTENEGRO, L.; PIOVESAN, M. R.; MACEDO, D. B.; CUNHA, M.; GUIMARAES, A.; RAMOS, C. O.; BENEDETTI, A. F. F.; LEAL, De Castro A.; GAGLIARDI, P. C.; ANTONINI, S. R.; GRYNGARTEN, M.; ARCARI, A. J.; ABREU, A. P.; KAISER, U. B.; SORIANO-GUILLEN, L.; ESCRIBANO-MUNOZ, A.; CORRIPIO, R.; I, J. Labarta; TRAVIESO-SUAREZ, L.; V, N. Ortiz-Cabrera; ARGENTE, J.; MENDONCA, B. B.; BRITO, V. N.; LATRONICO, A. C.
- Transcriptomic Response to 1,25-Dihydroxyvitamin D in Human Fibroblasts with or without a Functional Vitamin D Receptor (VDR): Novel Target Genes and Insights into VDR Basal Transcriptional Activity(2019) COSTA, Pedro L. F.; FRANCA, Monica M.; KATAYAMA, Maria L.; CARNEIRO, Eduardo T.; MARTIN, Regina M.; FOLGUEIRA, Maria A. K.; LATRONICO, Ana C.; FERRAZ-DE-SOUZA, BrunoThe vitamin D receptor (VDR) mediates vitamin D actions beyond bone health. While VDR activation by 1,25-dihydroxyvitamin D (1,25D) leads to robust transcriptional regulation, less is known about VDR actions in the absence of 1,25D. We analyzed the transcriptomic response to 1,25D in fibroblasts bearing a severe homozygous hereditary vitamin D resistant rickets-related p.Arg30* VDR mutation (MUT) and in control fibroblasts (CO). Roughly 4.5% of the transcriptome was regulated by 1,25D in CO fibroblasts, while MUT cells without a functional VDR were insensitive to 1,25D. Novel VDR target genes identified in human fibroblasts included bone and cartilage factors CILP, EFNB2, and GALNT12. Vehicle-treated CO and MUT fibroblasts had strikingly different transcriptomes, suggesting basal VDR activity. Indeed, oppositional transcriptional effects in basal conditions versus after 1,25D activation were implied for a subset of target genes mostly involved with cell cycle. Cell proliferation assays corroborated this conjectured oppositional basal VDR activity, indicating that precise 1,25D dosage in target tissues might be essential for modulating vitamin D actions in human health.
conferenceObject X-Linked Central Precocious Puberty Associated with MECP2 defects(2022) CANTON, Ana; TINANO, Flavia; GUASTI, Leonardo; MONTENEGRO, Luciana; RYAN, Fiona; SHEARS, Deborah; MELO, Maria Edna; GOMES, Larissa; PIANA, Mariana; BRAUNER, Raja; ESPINO, Rafael; ESCRIBANO-MUNOZ, Arancha; PAGANONI, Alyssa; KORBONITS, Marta; SERAPHIM, Carlos Eduardo; FARIA, Aline; COSTA, Silvia; KREPISCHI, Ana Cristina; JORGE, Alexander; DAVID, Alessia; ARGENTE, Jesus; MENDONCA, Berenice; BRITO, Vinicius; HOWARD, Sasha; LATRONICO, Ana Claudia- Retrospective Analysis of Prognostic Factors in Pediatric Patients with Adrenocortical Tumor from Unique Tertiary Center with Long-Term Follow-Up(2022) BACHEGA, Fernanda S.; V, Caio Suartz; ALMEIDA, Madson Q.; BRONDANI, Vania B.; CHARCHAR, Helaine L. S.; LACOMBE, Amanda M. F.; MARTINS-FILHO, Sebastiao N.; SOARES, Ibere C.; ZERBINI, Maria Claudia N.; DENES, Francisco T.; MENDONCA, Berenice; I, Roberto Lopes; LATRONICO, Ana Claudia; V, Maria Candida B. FragosoPediatric adrenocortical tumors (PACTs) represent rare causes of malignancies. However, the south/southeast regions of Brazil are known to have a high incidence of PACTs because of the founder effect associated with a germline pathogenic variant of tumor suppressor gene TP53. We aimed to retrospectively analyze the types of variables among hormone production, radiological imaging, tumor staging, histological and genetic features that were associated with the occurrence of malignancy in 95 patients (71% females) with PACTs from a unique center. The worst prognosis was associated with those aged > 3 years (p < 0.05), high serum levels of 11-desoxicortisol (p < 0.001), tumor weight >= 200 g (p < 0.001), tumor size >= 5 cm (p < 0.05), Weiss score >= 5 (p < 0.05), Wieneke index >= 3 (p < 0.001) and Ki67 >= 15% (p < 0.05). Furthermore, patients with MacFarlane stage IV had an overall survival rate almost two times shorter than patients with other stages (p < 0.001). Additionally, the subtractions of BUB1B-PINK1 (<6.95) expression (p < 0.05) and IGF-IR overexpression (p = 0.0001) were associated with malignant behavior. These results helped identify patients who are likely to have an aggressive course; further multicenter prospective studies are required to confirm our results. In conclusion, PACTs with these patterns of prognostic factors could be treated using an adjuvant approach that may improve the overall survival in such patients.
- 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.
conferenceObject Genetic evaluation in children with self-limited pubertal delay discloses new candidate genes(2023) REZENDE, Raissa; SCHAFER, Evan; KAISINGER, Lena; HE, Wen; ANDRADE, Nathalia; DANTAS, Naiara; CELLIN, Laurana; QUEDAS, Elisangela; PERRY, John; HOWARD, Sasha; LATRONICO, Ana Claudia; CHAN, Yee-Ming; JORGE, Alexander- The Congenital and Acquired Mechanisms Implicated in the Etiology of Central Precocious Puberty(2023) BRITO, Vinicius N.; CANTON, Ana P. M.; SERAPHIM, Carlos Eduardo; ABREU, Ana Paula; MACEDO, Delanie B.; MENDONCA, Berenice B.; KAISER, Ursula B.; ARGENTE, Jesus; LATRONICO, Ana ClaudiaThe etiology of central precocious puberty (CPP) is multiple and heterogeneous, including congenital and acquired causes that can be associated with structural or functional brain alterations. All causes of CPP culminate in the premature pulsatile secretion of hypothalamic GnRH and, consequently, in the premature reactivation of hypothalamic-pituitary-gonadal axis. The activation of excitatory factors or suppression of inhibitory factors during childhood represent the 2 major mechanisms of CPP, revealing a delicate balance of these opposing neuronal pathways. Hypothalamic hamartoma (HH) is the most well-known congenital cause of CPP with central nervous system abnormalities. Several mechanisms by which hamartoma causes CPP have been proposed, including an anatomical connection to the anterior hypothalamus, autonomous neuroendocrine activity in GnRH neurons, trophic factors secreted by HH, and mechanical pressure applied to the hypothalamus. The importance of genetic and/or epigenetic factors in the underlying mechanisms of CPP has grown significantly in the last decade, as demonstrated by the evidence of genetic abnormalities in hypothalamic structural lesions (eg, hamartomas, gliomas), syndromic disorders associated with CPP (Temple, Prader-Willi, Silver-Russell, and Rett syndromes), and isolated CPP from monogenic defects (MKRN3 and DLK1 loss-of-function mutations). Genetic and epigenetic discoveries involving the etiology of CPP have had influence on the diagnosis and familial counseling providing bases for potential prevention of premature sexual development and new treatment targets in the future. Global preventive actions inducing healthy lifestyle habits and less exposure to endocrine-disrupting chemicals during the lifespan are desirable because they are potentially associated with CPP.
- Prevalence of Deleterious Variants in MC3R in Patients With Constitutional Delay of Growth and Puberty(2023) DUCKETT, Katie; WILLIAMSON, Alice; KINCAID, John W. R.; RAINBOW, Kara; CORBIN, Laura J.; MARTIN, Hilary C.; EBERHARDT, Ruth Y.; HUANG, Qin Qin; HURLES, Matthew E.; HE, Wen; BRAUNER, Raja; DELANEY, Angela; DUNKEL, Leo; GRINSPON, Romina P.; HALL, Janet E.; HIRSCHHORN, Joel N.; HOWARD, Sasha R.; LATRONICO, Ana C.; JORGE, Alexander A. L.; MCELREAVEY, Ken; MERICQ, Veronica; MERINO, Paulina M.; PALMERT, Mark R.; PLUMMER, Lacey; REY, Rodolfo A.; REZENDE, Raissa C.; SEMINARA, Stephanie B.; SALNIKOV, Kathryn; BANERJEE, Indraneel; LAM, Brian Y. H.; PERRY, John R. B.; TIMPSON, Nicholas J.; CLAYTON, Peter; CHAN, Yee-Ming; ONG, Ken K.; O'RAHILLY, StephenContext The melanocortin 3 receptor (MC3R) has recently emerged as a critical regulator of pubertal timing, linear growth, and the acquisition of lean mass in humans and mice. In population-based studies, heterozygous carriers of deleterious variants in MC3R report a later onset of puberty than noncarriers. However, the frequency of such variants in patients who present with clinical disorders of pubertal development is currently unknown. Objective This work aimed to determine whether deleterious MC3R variants are more frequently found in patients clinically presenting with constitutional delay of growth and puberty (CDGP) or normosmic idiopathic hypogonadotropic hypogonadism (nIHH). Methods We examined the sequence of MC3R in 362 adolescents with a clinical diagnosis of CDGP and 657 patients with nIHH, experimentally characterized the signaling properties of all nonsynonymous variants found and compared their frequency to that in 5774 controls from a population-based cohort. Additionally, we established the relative frequency of predicted deleterious variants in individuals with self-reported delayed vs normally timed menarche/voice-breaking in the UK Biobank cohort. Results MC3R loss-of-function variants were infrequent but overrepresented in patients with CDGP (8/362 [2.2%]; OR = 4.17; P = .001). There was no strong evidence of overrepresentation in patients with nIHH (4/657 [0.6%]; OR = 1.15; P = .779). In 246 328 women from the UK Biobank, predicted deleterious variants were more frequently found in those self-reporting delayed (aged & GE;16 years) vs normal age at menarche (OR = 1.66; P = 3.90E-07). Conclusion We have found evidence that functionally damaging variants in MC3R are overrepresented in individuals with CDGP but are not a common cause of this phenotype.
conferenceObject Several new candidate genes for self-limited delayed puberty revealed by whole exome sequencing(2023) REZENDE, Raissa; SCHAFER, Evan; KAISINGER, Lena; DANTAS, Naiara; ANDRADE, Nathalia; CELLIN, Laurana; QUEDAS, Elisangela; HE, Wen; PERRY, John; XAVIER, Ana Claudia Latronico; HOWARD, Sasha; CHAN, Yee-Ming; JORGE, Alexander- Disorders of Sex Development and Hypogonadism: Genetics, Mechanism, and Therapies(2012) GUERRA-JUNIOR, Gil; LATRONICO, Ana Claudia; HIORT, Olaf; REY, Rodolfo