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
• City of the host institution: São Paulo
• Principal investigators: 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 ; Marcela Gonçalves Meirelles ; Mariana Camargo Maschietto ; Mariana Ferreira de Assis Funari ; Mirian Yumie Nishi ; Monica Malheiros França ; Nathalia Lisboa Rosa Almeida Gomes ; Rafael Henrique Nóbrega ; 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): 26/04558-6 - Genetic characterization of the dhx37 gene in zebrafish as a model for the study of gonadal development., BP.IC; 26/00472-0 - Expression of dhx37 During Sexual Differentiation in Zebrafish: A High-Resolution In Situ Hybridization (RNAscope) Approach, BP.IC; 25/26283-6 - Standardization and Application of C19 Classic and C19 11-Oxygenated Steroid Profile Determination in Patients with Premature Pubarche and Virilizing Congenital Adrenal Hyperplasia, BP.IC; + associated scholarships 25/24569-0 - Technical training for preparing libraries for large-scale sequencing using Miseq, Nextseq550, and Nextseq2000 equipment., BP.TT; 25/07534-8 - FUNCTIONAL RESCUE OF PATHOGENIC VARIANTS IN AMH AND DHX37 GENES USING ZEBRAFISH MODEL, BP.PD; 25/10833-7 - Temporal Analysis of the Expression of Genes Involved in Gonadal Differentiation in Dhx37 and Amh Mutant Zebrafish., BP.IC; 25/05439-8 - Study of the MicroRNA Expression Profile in Gonads of Patients with 46,XX Ovotesticular Difference of Sexual Development., BP.DD; 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; 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

(12)

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

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)

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)

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)

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)

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 LOCH; NAKAGUMA, MARILENA; TAVARES, LEONARDO ANDRADE GONTIJO; BATATINHA, JULIO AMERICO PEREIRA; NISHI, MIRIAN YUMIE; DOMENICE, SORAHIA; PADULA, MARIO; MENDONCA, BERENICE BILHARINHO. Hypopituitarism and Rathke's cleft cyst in 48,XXYY Syndrome: new insights into sex chromosome aneuploidies. Einstein (São Paulo), v. 23, p. 5-pg., 2025-01-01. (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)

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)

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)

HORNIG, NADINE; BATISTA, RAFAEL LOCH. Androgen insensitivity and the evolving genetic heterogeneity. BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM, v. 39, n. 4, p. 9-pg., 2025-07-01. (19/26780-9)