New perspectives of the genetic study of idiopathic central precocious puberty

• Grant number: 13/06391-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2013
• End date: April 30, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ana Claudia Latronico Xavier
• Grantee: Francisca Delanie Bulcão de Macêdo
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Most cases of Central Precocious Puberty (CPP) remains idiopathic. The hypothesis of a genetic cause has been strengthened by the discovery of some genes associated with this phenotype, especially those involved with the kisspeptin system (KISS1 and GPR54). However, only a minority of cases of CPP could be explained by mutations in these genes. Recently, animal models LSD1 haploinsufficient (LSD + / -) showed some markers of sexual precocity and an increased expression of kisspeptin and neurokinin B in vivo and in vitro, suggesting that this gene may be implicated in the phenotype of the CPP in humans. Objectives: Clinical and genetic characterization of patients with familial and sporadic CPP (idiopathic). Patients and Methods: 31 patients with familial CPP (17 families) and 82 sporadic cases. The analysis of mutations and polymorphisms of LSD1 in patients with familial and sporadic CPP will be performed by the automatic sequencing (Sanger). More modern techniques of molecular biology, such as CGH (Agilent Technologies, Santa Clara CA 95051, United States) and exomic sequencing (ILLUMNA-Clonal Single Molecule Array technology - CSMA) will be used to identify potential abnormalities in the genome of children with familial CPP. (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)

LUDWIG, NATASHA G.; RADAELI, RAFAEL F.; DA SILVA, MARIANA M. X.; ROMERO, CAMILA M.; CARRILHO, ALEXANDRE J. F.; BESSA, DANIELLE; MACEDO, DELANIE B.; DE OLIVEIRA, MARIA L.; LATRONICO, ANA CLAUDIA; MAZZUCO, TANIA L.. A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 60, n. 6, p. 596-600, NOV-DEC 2016. (13/06391-1)

DELANIE B. MACEDO; PRISCILLA CUKIER; BERENICE B. MENDONCA; ANA CLAUDIA LATRONICO; VINICIUS NAHIME BRITO. Avanços na etiologia, no diagnóstico e no tratamento da puberdade precoce central. Arquivos Brasileiros de Endocrinologia e Metabologia, v. 58, n. 2, p. 108-117, 2014-03-00. (13/06391-1)

MACEDO, DELANIE B.; FRANCA, MONICA M.; MONTENEGRO, LUCIANA R.; CUNHA-SILVA, MARINA; BEST, DANIELLE S.; ABREU, ANA PAULA; KAISER, URSULA B.; MENDONCA, BERENICE B.; JORGE, ALEXANDER A. L.; BRITO, VINICIUS N.; et al. Central Precocious Puberty Caused by a Heterozygous Deletion in the MKRN3 Promoter Region. Neuroendocrinology, v. 107, n. 2, p. 127-132, 2018. (13/03236-5, 13/06391-1)

MACEDO, DELANIE B.; ABREU, ANA PAULA; REIS, ANA CLAUDIA S.; MONTENEGRO, LUCIANA R.; DAUBER, ANDREW; BENEDUZZI, DAIANE; CUKIER, PRISCILLA; SILVEIRA, LETICIA F. G.; TELES, MILENA G.; CARROLL, RONA S.; et al. Central Precocious Puberty That Appears to Be Sporadic Caused by Paternally Inherited Mutations in the Imprinted Gene Makorin Ring Finger 3. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. 99, n. 6, p. E1097-E1103, JUN 2014. (13/06391-1, 05/04726-0)

BESSA, DANIELLE S.; MACEDO, DELANIE B.; BRITO, VINICIUS N.; FRANCA, MONICA M.; MONTENEGRO, LUCIANA R.; CUNHA-SILVA, MARINA; SILVEIRA, LETICIA G.; HUMMEL, TIAGO; BERGADA, IGNACIO; BRASLAVSKY, DEBORA; et al. High Frequency of MKRN3 Mutations in Male Central Precocious Puberty Previously Classified as Idiopathic. Neuroendocrinology, v. 105, n. 1, p. 17-25, 2017. (13/03236-5, 13/06391-1)

DAUBER, ANDREW; CUNHA-SILVA, MARINA; MACEDO, DELANIE B.; BRITO, VINICIUS N.; ABREU, ANA PAULA; ROBERTS, STEPHANIE A.; MONTENEGRO, LUCIANA R.; ANDREW, MELISSA; KIRBY, ANDREW; WEIRAUCH, MATTHEW T.; et al. Paternally Inherited DLK1 Deletion Associated With Familial Central Precocious Puberty. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. 102, n. 5, p. 1557-1567, MAY 1 2017. (13/03236-5, 13/06391-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MACÊDO, Francisca Delanie Bulcão de. Inactivating mutations in the MKRN3 gene are cause of familial central precocious puberty. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.