Molecular and epigenetic research on Differences in Sexual Development (DSD): impact of scientific diffusion on the relationship between science and society

• Grant number: 19/26780-9
• Support Opportunities: Research Projects - Thematic Grants
• Start date: December 01, 2021
• End date: November 30, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Berenice Bilharinho de Mendonça
• Grantee: Berenice Bilharinho de Mendonça
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Luciani Renata Silveira de Carvalho ; Sorahia Domenice ; Tania Aparecida Sartori Sanchez Bachega
• Associated researchers: Ana Cristina Victorino Krepischi ; Elaine Maria Frade Costa ; Gil Guerra Júnior ; Helena Panteliou Lima Valassi ; Mariana Camargo Maschietto ; Mariana Ferreira de Assis Funari ; Mirian Yumie Nishi ; Monica Malheiros França ; Nathalia Lisboa Rosa Almeida Gomes ; Rafael Loch Batista ; Raquel Martinez Ramos ; Vinicius Nahime de Brito
• Associated research grant(s): 21/15079-8 - Multi-user equipment approved in grant 2019/26780-9 - nextseq 2000 sequencer e infinium hd starter kit, AP.EMU
• Associated scholarship(s): 24/23694-2 - DIFERENTIATION OF GONADAL CELLS FROM iPSCs TO STUDY DIFFERENCES OF SEXUAL DEVELOPMENT, BP.PD; 23/16309-2 - Cardiovascular risk assessment in patients with classical 21-hydroxylase deficiency: the impact of hyperandrogenism and glucocorticoid therapy on high-density lipoprotein (HDL) functionality, BP.DD; 23/16302-8 - Assessment of cardiovascular risk in patients with the non-classical form of congenital adrenal hyperplasia, with emphasis on the functionality of the HDL particle, based on specific therapeutic modalities, BP.DD; + associated scholarships 23/10426-7 - Systematic approach and diagnosis of 46, XY differences of sex development: molecular investigation and APP development, BP.DD; 23/09534-0 - Use of Zebrafish (Danio rerio) as an animal model to elucidate the functional effect of allelic variants identified in patients with differences in sexual development, BP.PD; 22/06089-2 - COMPARISON OF THE GLOBAL METHYLATION PROFILES OF PATIENTS WITH SILVER-RUSSELL SYNDROME AND SMALL FOR GESTATIONAL AGE BORN WITH AND WITHOUT ATYPICAL GENITALY, BP.DR; 22/08852-5 - Molecular and Epigenetic Investigation of Differences in Sexual Development (DSD): Impact of Scientific Dissemination on the Relationship between Science and Society., BP.JC - associated scholarships

Abstract

Differences of Sex Development (DSD) represent a set of congenital diseases in which the development of chromosomal, gonadal, or anatomical sex is atypical. Current knowledge allows molecular diagnosis in only about 50% of patients. New mechanisms of gene regulation are emerging in novel causes of DSD and explaining different phenotypes caused by the same gene mutation. The identification of the molecular causes of DSDs increases the knowledge of gonadal determination mechanisms. In this project, we will use new resources to address the human genome in order to (1) identify new candidate genes as the cause of 46, XY DDS and 46, XX DDS by sequencing the entire exome; (2) to investigate the role of epigenetic mechanisms (methylation and miRNA) in the etiology and phenotype modulation of patients with DSD 46, XX and 46, XY. (AU)

Scientific publications

(10)

(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)

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 CLAUDIA. The Congenital and Acquired Mechanisms Implicated in the Etiology of Central Precocious Puberty. ENDOCRINE REVIEWS, v. N/A, p. 29-pg., 2022-08-05. (22/00719-4, 19/26780-9)

SIRCILI, MARIA HELENA PALMA; BATISTA, RAFAEL LOCH; BARRETO, ENOCH QUINDERE DE SA; BUENO, SOLANGE PAIVA; BENEDETTI, ANNA FLAVIA FIGUEREDO; CRAVEIRO, FLORA LADEIRA; RAMOS, RAQUEL MATINEZ; MONTEIRO FILHO, MARCELO PRAXEDES; DOMENICE, SORAHIA; MENDONCA, BERENICE BILHARINHO; et al. Neonatal Hydrocolpos in Bardet-Biedl Syndrome due to a Novel Frameshift Indel in the BBS10 Gene. SEXUAL DEVELOPMENT, v. N/A, p. 6-pg., 2024-09-09. (19/26780-9)

FERRARI, MARIA TEREZA MARTINS; SILVA, ELINAELMA SUELANE DO NASCIMENTO; NISHI, MIRIAN YUMIE; BATISTA, RAFAEL LOCH; MENDONCA, BERENICE BILHARINHO; DOMENICE, SORAHIA. Testicular differentiation in 46,XX DSD: an overview of genetic causes. FRONTIERS IN ENDOCRINOLOGY, v. 15, p. 18-pg., 2024-04-24. (19/26780-9)

COSTA, FERNANDA CAVALIERI; GOMES, LARISSA GARCIA; DE LIMA, THAIS MARTINS; BORTOLOTTO, LUIZ APARECIDO; HONG, VALERIA; VERARDINO, RENATA; ROCHA, MANOEL DE SOUZA; UEDA, SERLI KIYOMI NAKAO; DE MIRANDA, MIRELA COSTA; DE SOUZA, HERALDO POSSOLO; et al. Cardiovascular Risk in Women With Nonclassical Congenital Adrenal Hyperplasia. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. N/A, p. 8-pg., 2024-03-11. (19/26780-9)

RAMOS, RAQUEL MARTINEZ; PETROLI, REGINALDO JOSE; D'ALESSANDRE, NATHALIA DA ROZ; GUARDIA, GABRIELA DER AGOPIAN; AFONSO, ANA CAROLINE DE FREITAS; NISHI, MIRIAN YUMIE; DOMENICE, SORAHIA; GALANTE, PEDRO ALEXANDRE FAVORETTO; MENDONCA, BERENICE BILHARINHO; BATISTA, RAFAEL LOCH. Small Indels in the Androgen Receptor Gene: Phenotype Implications and Mechanisms of Mutagenesis. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. 109, n. 1, p. 12-pg., 2023-12-21. (19/26780-9)

GIULIATTI, SILVANA; BENEDETTI, ANNA FLAVIA FIGUEREDO; RAMOS, RAQUEL MARTINEZ; PETROLI, REGINALDO JOSE; DOMENICE, SORAHIA; MENDONCA, BERENICE BILHARINHO; BATISTA, RAFAEL LOCH. Hydropathic AF-2 variants in the androgen receptor gene among androgen insensitivity patients. ANDROLOGY, v. N/A, p. 12-pg., 2024-06-26. (19/26780-9)

BATISTA, RAFAEL L.; MENDONCA, BERENICE B.. The Molecular Basis of 5 alpha-Reductase Type 2 Deficiency. SEXUAL DEVELOPMENT, v. 16, n. 2-3, p. 13-pg., 2022-07-06. (19/26780-9)

BATISTA, RAFAEL LOCH; CRAVEIRO, FLORA LADEIRA; RAMOS, RAQUEL MARTINEZ; MENDONCA, BERENICE BILHARINHO. Mild Androgen Insensitivity Syndrome: The Current Landscape. ENDOCRINE PRACTICE, v. 28, n. 9, p. 7-pg., 2022-09-05. (19/26780-9)

RAFAEL LOCH BATISTA; MARLENE INÁCIO; VINICIUS NAHIME BRITO; MARIA HELENA PALMA SIRCILI; MIN JEONG BAG; NATHÁLIA LISBOA GOMES; ELAINE MARIA FRADE COSTA; SORAHIA DOMENICE; BERENICE BILHARINHO MENDONCA. Sexuality and fertility desire in a large cohort of individuals with 46, XY differences in sex development. Clinics, v. 78, 2023-05-19. (19/26780-9)

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)