Looking for new etiologies of central precocious puberty

• Grant number: 21/14687-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2022
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Ana Claudia Latronico Xavier
• Grantee: Aline Almeida Bastos
• 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

Precocious puberty occurs when the development of secondary sexual characteristics occurs before 8 years of old in girls and before 9 years old in boys. The most common mechanism of precocious puberty is the premature activation of pulsatile GnRH secretion, characterized as Central Precocious Puberty (CPP). Recent studies have allowed further elucidation of the etiology of Precocious Puberty (PP). More recently, studies with Endocrine Disruptors (ED), with emphasis on mercury, point out its role in the activation of the reproductive axis, which can lead to CPP. Objectives: To review Magnetic Resonance (MR) images of patients with affected CPP. Perform genetic analysis through global exomic sequencing of patients with sporadic and familial CPP. To assess the role of mercury concentrations in patients with CPP without defined structural or genetic alterations in the central nervous system. Methodology: Patients with CPP (50 cases) will be recruited from the pubertal disorders clinic at the Hospital das Clínicas at FMUSP and from collaborating centers. Genetic analysis and investigation of mercury concentrations will be performed in all selected patients with CPP. Mercury concentrations will be measured in blood, urine and hair. Human hair samples (200 strands of hair) will be analyzed by the Milestone Direct Mercury Analyzer method (DMA-80, Milestone Inc., Shelton, CT, USA), using the EPA 7473 method. The reference values used will be 1-2, 3¼g/g of capillary mercury, 5-10¼g/L of mercury in blood and urine 50 ¼g/g urinary creatinine. The genetic research will be carried out at the SELA laboratory of the Faculty of Medicine, University of São Paulo, using the molecular cloning technology IlluminaHiSeq 2000 (IlluminaInc, San Diego, CA). Each variant found will be classified according to the American College of Medical Genetics and Genomics guidelines into: "pathogenic", "probably pathogenic", "undetermined meaning". Justification: Our study aims to increase knowledge about the etiologies of CPP, contributing to the diagnosis, and thus enabling earlier treatment of cases or institution of preventive measures, as in the case of exposure to ED´s. (AU)