| Full text | |
| Author(s): |
Canton, Ana Pinheiro Machado
;
Seraphim, Carlos Eduardo
;
Montenegro, Luciana Ribeiro
;
Krepischi, Ana Cristina Victorino
;
Mendonca, Berenice Bilharinho
;
Latronico, Ana Claudia
;
Brito, Vinicius Nahime
Total Authors: 7
|
| Document type: | Journal article |
| Source: | EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 190, n. 6, p. 10-pg., 2024-06-26. |
| Abstract | |
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) | |
| FAPESP's process: | 19/26780-9 - Molecular and epigenetic research on Differences in Sexual Development (DSD): impact of scientific diffusion on the relationship between science and society |
| Grantee: | Berenice Bilharinho de Mendonça |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 22/00719-4 - Comprehensive genetic and epigenetic investigation of patients with syndromic central precocious puberty |
| Grantee: | Ana Pinheiro Machado Canton |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 19/27631-7 - Genetic and epigenetic studies of endocrine disorders related with reproductive axis |
| Grantee: | Ana Claudia Latronico Xavier |
| Support Opportunities: | Research Projects - Thematic Grants |