The genetic etiology is a relevant cause of central precocious puberty

Autor(es)

Canton, Ana Pinheiro Machado ; Seraphim, Carlos Eduardo ; Montenegro, Luciana Ribeiro ; Krepischi, Ana Cristina Victorino ; Mendonca, Berenice Bilharinho ; Latronico, Ana Claudia ; Brito, Vinicius Nahime

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 190, n. 6, p. 10-pg., 2024-06-26.

Resumo

Objectives The etiology of central precocious puberty (CPP) has expanded with identification of new genetic causes, including the monogenic deficiency of Makorin-Ring-Finger-Protein-3 (MKRN3). We aimed to assess the prevalence of CPP causes and the predictors of genetic involvement in this phenotype.Design A retrospective cohort study for an etiological survey of patients with CPP from a single academic center.Methods All patients with CPP had detailed medical history, phenotyping, and brain magnetic resonance imaging (MRI); those with negative brain MRI (apparently idiopathic) were submitted to genetic studies, mainly DNA sequencing studies, genomic microarray, and methylation analysis.Results We assessed 270 patients with CPP: 50 (18.5%) had CPP-related brain lesions (34 [68%] congenital lesions), whereas 220 had negative brain MRI. Of the latter, 174 (165 girls) were included for genetic studies. Genetic etiologies were identified in 22 patients (20 girls), indicating an overall frequency of genetic CPP of 12.6% (22.2% in boys and 12.1% in girls). The most common genetic defects were MKRN3, Delta-Like-Non-Canonical-Notch-Ligand-1 (DLK1), and Methyl-CpG-Binding-Protein-2 (MECP2) loss-of-function mutations, followed by 14q32.2 defects (Temple syndrome). Univariate logistic regression identified family history (odds ratio [OR] 3.3; 95% CI 1.3-8.3; P = .01) and neurodevelopmental disorders (OR 4.1; 95% CI 1.3-13.5; P = .02) as potential clinical predictors of genetic CPP.Conclusions Distinct genetic causes were identified in 12.6% patients with apparently idiopathic CPP, revealing the genetic etiology as a relevant cause of CPP in both sexes. Family history and neurodevelopmental disorders were suggested as predictors of genetic CPP. We originally proposed an algorithm to investigate the etiology of CPP including genetic studies. (AU)

• Processo FAPESP: 19/26780-9 - Investigação molecular e epigenética das Diferenças do Desenvolvimento Sexual (DDS): impacto da divulgação científica na relação entre ciência e sociedade
• Beneficiário: Berenice Bilharinho de Mendonça
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 22/00719-4 - Ampla investigação genética e epigenética de pacientes com puberdade precoce central sindrômica
• Beneficiário: Ana Pinheiro Machado Canton
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/27631-7 - Estudos genéticos e epigenéticos dos distúrbios endócrinos do eixo reprodutivo
• Beneficiário: Ana Claudia Latronico Xavier
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/50137-5 - Caracterização molecular de doenças monogênicas do desenvolvimento por sequenciamento em larga escala
• Beneficiário: Berenice Bilharinho de Mendonça
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários