ANA CLAUDIA LATRONICO XAVIER
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
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- High Frequency of MKRN3 Mutations in Male Central Precocious Puberty Previously Classified as Idiopathic(2017) 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; ABREU, Ana Paula; DAUBER, Andrew; MENDONCA, Berenice B.; KAISER, Ursula B.; LATRONICO, Ana ClaudiaBackground/Aims: Recently, loss-of-function mutations in the MKRN3 gene have been implicated in the etiology of familial central precocious puberty (CPP) in both sexes. We aimed to analyze the frequency of MKRN3 mutations in boys with CPP and to compare the clinical and hormonal features of boys with and without MKRN3 mutations. Methods: This was a retrospective review of clinical, hormonal and genetic features of 20 male patients with idiopathic CPP evaluated at an academic medical center. The entire coding regions of MKRN3, KISS1 and KISS1R genes were sequenced. Results: We studied 20 boys from 17 families with CPP. All of them had normal brain magnetic resonance imaging. Eight boys from 5 families harbored four distinct heterozygous MKRN3 mutations predicted to be deleterious for protein function, p.Ala162Glyfs*14, p.Arg213Glyfs*73, p.Arg328Cys and p. Arg365Ser. One boy carried a previously described KISS1-activating mutation (p.Pro74Ser). The frequency of MKRN3 mutations among these boys with idiopathic CPP was significantly higher than previously reported female data (40 vs. 6.4%, respectively, p < 0.001). Boys with MKRN3 mutations had typical clinical and hormonal features of CPP. Notably, they had later pubertal onset than boys without MKRN3 abnormalities (median age 8.2 vs. 7.0 years, respectively, p = 0.033). Conclusion: We demonstrated a high frequency of MKRN3 mutations in boys with CPP, previously classified as idiopathic, suggesting the importance of genetic analysis in this group. The boys with CPP due to MKRN3 mutations had classical features of CPP, but with puberty initiation at a borderline age. (C) 2016 S. Karger AG, Basel
- Genotype-Phenotype Correlations in Central Precocious Puberty Caused by MKRN3 Mutations(2021) SERAPHIM, Carlos Eduardo; CANTON, Ana Pinheiro Machado; MONTENEGRO, Luciana; PIOVESAN, Maiara Ribeiro; MACEDO, Delanie B.; CUNHA, Marina; GUIMARAES, Aline; RAMOS, Carolina Oliveira; BENEDETTI, Anna Flavia Figueiredo; LEAL, Andrea de Castro; GAGLIARDI, Priscila C.; ANTONINI, Sonir R.; GRYNGARTEN, Mirta; ARCARI, Andrea J.; ABREU, Ana Paula; KAISER, Ursula B.; SORIANO-GUILLEN, Leandro; ESCRIBANO-MUNOZ, Arancha; CORRIPIO, Raquel; I, Jose Labarta; TRAVIESO-SUAREZ, Lourdes; ORTIZ-CABRERA, Nelmar Valentina; ARGENTE, Jesus; MENDONCA, Berenice B.; BRITO, Vinicius N.; LATRONICO, Ana ClaudiaContext: Loss-of-function mutations of makorin RING finger protein 3 (MKRN3) are the most common monogenic cause of familial central precocious puberty (CPP). Objective: To describe the clinical and hormonal features of a large cohort of patients with CPP due to MKRN3 mutations and compare the characteristics of different types of genetic defects. Methods: Multiethnic cohort of 716 patients with familial or idiopathic CPP screened for MKRN3 mutations using Sanger sequencing. A group of 156 Brazilian girls with idiopathic CPP (ICPP) was used as control group. Results: Seventy-one patients (45 girls and 26 boys from 36 families) had 18 different loss-of-function MKRN3 mutations. Eight mutations were classified as severe (70% of patients). Among the 71 patients, first pubertal signs occurred at 6.2 +/- 1.2 years in girls and 7.1 +/- 1.5 years in boys. Girls with MKRN3 mutations had a shorter delay between puberty onset and first evaluation and higher follicle-stimulating hormone levels than ICPP. Patients with severe MKRN3 mutations had a greater bone age advancement than patients with missense mutations (2.3 +/- 1.6 vs 1.6 +/- 1.4 years, P =.048), and had higher basal luteinizing hormone levels (2.2 +/- 1.8 vs 1.1 +/- 1.1 UI/L, P =.018) at the time of presentation. Computational protein modeling revealed that 60% of the missense mutations were predicted to cause protein destabilization. Conclusion: Inherited premature activation of the reproductive axis caused by loss-of-function mutations of MKRN3 is clinically indistinct from ICPP. However, the type of genetic defect may affect bone age maturation and gonadotropin levels.
conferenceObject Long-Term Outcome In Leydig Cell Hypoplasia(2019) BONCOMPAGNI, Alessandra; BRYCE, Jillian; LUCACCIONI, Laura; IUGHETTI, Lorenzo; ACERINI, Carlo; CUCCARO, Rieko T.; BERTELLONI, Silvano; HANNEMA, Sabine E.; DARENDELILER, F. Feyza; POYRAZOGLU, Sukran; DENZER, Friederike; BATISTA, Rafael L.; DOMENICE, Sorahia; LATRONICO, Ana C.; MENDONCA, Berenice B.; REY, Rodolfo; AHMED, S. Faisal