Genetic and epigenetic studies of endocrine disorders related with reproductive axis

• Grant number: 19/27631-7
• Support Opportunities: Research Projects - Thematic Grants
• Start date: June 01, 2021
• End date: May 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ana Claudia Latronico Xavier
• Grantee: Ana Claudia Latronico Xavier
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Vinicius Nahime de Brito
• Associated researchers: Ana Cristina Victorino Krepischi ; Larissa Garcia Gomes ; Luciana Ribeiro Montenegro ; Nadja Cristhina de Souza Pinto ; Niels Olsen Saraiva Câmara
• Associated research grant(s): 24/07058-9 - Endocrine Society Annual Meeting - ENDO 2024, AR.EXT
• Associated scholarship(s): 23/16890-7 - Association between Polycystic Ovary Syndrome and Central Precocious Puberty and its impact on reproductive and metabolic outcomes: a clinical and genetic study of the largest Brazilian multicenter cohort (ELSA Brasil), BP.PD; 22/15182-6 - Analysis of the MKRN3 gene in children with familial or sporadic central precocious puberty, BP.IC; 23/03773-2 - Investigation of mechanisms of action for DLK1 on GnRH hypothalamic secretion and metabolic pathways, BP.PD; + associated scholarships 22/00847-2 - Clinical, laboratory and evaluative aspects of patients with isolated premature thelarche, BP.IC; 22/00719-4 - Comprehensive genetic and epigenetic investigation of patients with syndromic central precocious puberty, BP.PD; 21/14687-4 - Looking for new etiologies of central precocious puberty, BP.DD; 21/12205-2 - Investigation of genetic basis of Familial Central Precocious Puberty of maternal inheritance, BP.DD - associated scholarships

Abstract

Disorders of the reproductive axis are classically grouped according to their origin (central/secondary or peripheral/primary) and commonly determine relevant impairments in the individual's hormonal, reproductive and psychological health at all stages of life. The etiology of several congenital diseases involving the hypothalamic-pituitary region, such as central and peripheral precocious puberty were mainly clarified from the investigation of gene mutations using classical DNA sequencing techniques (Sanger method) and more recently large-scale sequencing. Despite these accomplishments, many diseases of the reproductive axis remain with their etiology still unknown (idiopathic). More recently, the possibility of epigenetic changes, including methylation defects, has been suggested as causal factors of these conditions. In the current research project, we have gathered 6 different original proposals for genetic and epigenetic studies, using robust and advanced methodologies applied to large cohorts (500 index patients) with disorders of the reproductive axis, including central or peripheral precocious puberty due to ovarian autonomy (McCune Albright) and polycystic ovary syndrome. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CANTON, ANA PINHEIRO MACHADO; MACEDO, DELANIE BULCAO; ABREU, ANA PAULA; LATRONICO, ANA CLAUDIA. Genetics and Epigenetics of Human Pubertal Timing: The Contribution of Genes Associated With Central Precocious Puberty. JOURNAL OF THE ENDOCRINE SOCIETY, v. 9, n. 2, p. 10-pg., 2025-01-21. (22/00719-4, 19/27631-7)

TINANO, FLAVIA REZENDE; CANTON, ANA PINHEIRO MACHADO; MONTENEGRO, LUCIANA R.; DE CASTRO LEAL, ANDREA; FARIA, ALINE G.; SERAPHIM, CARLOS E.; BRAUNER, RAJA; JORGE, ALEXANDER A.; MENDONCA, BERENICE B.; ARGENTE, JESUS; et al. Clinical and Genetic Characterization of Familial Central Precocious Puberty. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. N/A, p. 10-pg., 2023-01-06. (22/00719-4, 19/27631-7, 21/12205-2)

MONTENEGRO, LUCIANA; SERAPHIM, CARLOS; TINANO, FLAVIA; PIOVESAN, MAIARA; CANTON, ANA P. M.; MCELREAVEY, KEN; BRABANT, SEVERINE; BORIS, NATALIA P.; MAGNUSON, MELISSA; CARROLL, RONA S.; et al. Familial central precocious puberty due to DLK1 deficiency: novel genetic findings and relevance of serum DLK1 levels. EUROPEAN JOURNAL OF ENDOCRINOLOGY, v. 189, n. 3, p. 7-pg., 2023-09-01. (22/04870-9, 21/12205-2, 19/27631-7, 22/00719-4)

PIOVESAN, MAIARA; MACENA, LARISSA BARACHO; JORGE, ALEXANDER DE LIMA; LIMA-VALASSI, HELENA PANTELIOU; CANTON, ANA PINHEIRO MACHADO; MENDONCA, BERENICE B.; LATRONICO, ANA CLAUDIA; BRITO, VINICIUS NAHIME; MONTENEGRO, LUCIANA RIBEIRO. Genetic Investigation of Regulatory Regions of MKRN3 and DLK1 Genes in Children with Central Precocious Puberty. Hormone Research in Paediatrics, v. N/A, p. 8-pg., 2024-12-20. (17/23892-5, 19/27631-7)

CANTON, ANA PINHEIRO MACHADO; SERAPHIM, CARLOS EDUARDO; MONTENEGRO, LUCIANA RIBEIRO; KREPISCHI, ANA CRISTINA VICTORINO; MENDONCA, BERENICE BILHARINHO; LATRONICO, ANA CLAUDIA; BRITO, VINICIUS NAHIME. The genetic etiology is a relevant cause of central precocious puberty. EUROPEAN JOURNAL OF ENDOCRINOLOGY, v. 190, n. 6, p. 10-pg., 2024-06-26. (19/26780-9, 22/00719-4, 19/27631-7)

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.. High-throughput Sequencing to Identify Monogenic Etiologies in a Preselected Polycystic Ovary Syndrome Cohort. JOURNAL OF THE ENDOCRINE SOCIETY, v. 6, n. 9, p. 10-pg., 2022-09-01. (15/17350-0, 19/27631-7)