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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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
Total Authors: 15
Document type: Journal article
Source: Neuroendocrinology; v. 105, n. 1, p. 17-25, 2017.
Web of Science Citations: 15

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)

FAPESP's process: 13/03236-5 - New approaches and methodologies in molecular-genetic studies of growth and pubertal development disorders
Grantee:Alexander Augusto de Lima Jorge
Support type: Research Projects - Thematic Grants
FAPESP's process: 13/06391-1 - New perspectives of the genetic study of idiopathic central precocious puberty
Grantee:Francisca Delanie Bulcão de Macêdo
Support type: Scholarships in Brazil - Doctorate (Direct)