Comprehensive genetic and epigenetic investigation of patients with syndromic central precocious puberty

• Grant number: 22/00719-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2022
• End date: March 31, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ana Claudia Latronico Xavier
• Grantee: Ana Pinheiro Machado Canton
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/27631-7 - Genetic and epigenetic studies of endocrine disorders related with reproductive axis, AP.TEM

Abstract

Distinct studies have shown the participation of (epi)genetic mechanisms in the human pubertal control. The recognition of genetic causes of central precocious puberty (CPP) have increased, especially with the identification of mutations in two imprinted genes (MKRN3 and DLK1) in familial cases of non-syndromic CPP. Both genes are located at critical regions of (epi)genetic syndromes known to have CPP in their clinical spectrum (Prader-Willi syndrome and Temple syndrome, respectively). Other congenital etiologies might be elucidated based on an integrative clinical-genetic approach. The purpose of this project is to investigate patients with syndromic CPP with or without central nervous system lesions through high resolution and large-scale genetic studies and to elucidate possible genes/loci implicated in the human puberty. MECP2 is an X-linked gene playing a role in the transcription regulation of multiple genes relevant for the neurologic development. MECP2 loss-of-function mutations are usually associated with neurodevelopmental disorders, mainly with Rett syndrome. The typical Rett syndrome is characterized by regression of the neuropsychomotor acquired skills. Early pubertal development has been demonstrated in girls with Rett syndrome. In this context, this project proposes the genetic investigation of MECP2 gene in patients with CPP.

Scientific publications

(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)

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)

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)