Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

High Frequency of MKRN3 Mutations in Male Central Precocious Puberty Previously Classified as Idiopathic

Texto completo
Autor(es):
Mostrar menos -
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 Claudia
Número total de Autores: 15
Tipo de documento: Artigo Científico
Fonte: Neuroendocrinology; v. 105, n. 1, p. 17-25, 2017.
Citações Web of Science: 18
Resumo

Background/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 (AU)

Processo FAPESP: 13/03236-5 - Novas abordagens e metodologias na investigação genético-molecular dos distúrbios de crescimento e desenvolvimento puberal
Beneficiário:Alexander Augusto de Lima Jorge
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 13/06391-1 - Novas perspectivas no estudo genético da puberdade precoce central idiopática
Beneficiário:Francisca Delanie Bulcão de Macêdo
Linha de fomento: Bolsas no Brasil - Doutorado Direto