作者
Ana Paula Abreu, Andrew Dauber, Delanie B Macedo, Sekoni D Noel, Vinicius N Brito, John C Gill, Priscilla Cukier, Iain R Thompson, Victor M Navarro, Priscila C Gagliardi, Tânia Rodrigues, Cristiane Kochi, Carlos Alberto Longui, Dominique Beckers, Francis de Zegher, Luciana R Montenegro, Berenice B Mendonca, Rona S Carroll, Joel N Hirschhorn, Ana Claudia Latronico, Ursula B Kaiser
发表日期
2013/6/27
期刊
New England Journal of Medicine
卷号
368
期号
26
页码范围
2467-2475
出版商
Massachusetts Medical Society
简介
Background
The onset of puberty is first detected as an increase in pulsatile secretion of gonadotropin-releasing hormone (GnRH). Early activation of the hypothalamic–pituitary–gonadal axis results in central precocious puberty. The timing of pubertal development is driven in part by genetic factors, but only a few, rare molecular defects associated with central precocious puberty have been identified.
Methods
We performed whole-exome sequencing in 40 members of 15 families with central precocious puberty. Candidate variants were confirmed with Sanger sequencing. We also performed quantitative real-time polymerase-chain-reaction assays to determine levels of messenger RNA (mRNA) in the hypothalami of mice at different ages.
Results
We identified four novel heterozygous mutations in MKRN3, the gene encoding makorin RING-finger protein 3, in 5 of the 15 families; both sexes were affected. The …
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AP Abreu, A Dauber, DB Macedo, SD Noel, VN Brito… - New England Journal of Medicine, 2013