New Causes of Central Precocious Puberty: The Role of Genetic Factors
New Causes of Central Precocious Puberty: The Role of Genetic Factors
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DOI：
10.1159/000366282
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发表时间：
2014-01-01
影响因子：
4.1
通讯作者：
Latronico, Ana Claudia
中科院分区：
文献类型：
--
作者：
Macedo, Delanie Bulcao;Brito, Vinicius Nahime;Latronico, Ana Claudia
人类青春期开始的一个关键事件是下丘脑神经元再次脉冲性释放促性腺激素释放激素（GnRH）。通过研究动物模型和患有生殖障碍的人类，已经发现了控制GnRH个体发育和生理学的途径。最近的人体研究表明，在GnRH分泌的过早再激活中，kisspeptin及其同源受体（KISS 1/KISS 1 R）的激活和MKRN 3的失活导致中枢性性早熟（CPP）。MKRN 3是位于15号染色体长臂上的印记基因，编码makorin环指蛋白3，其参与泛素化和细胞信号传导。MKRN 3蛋白质仅来源于由于母体印记而从父系遗传的基因拷贝转录的RNA。目前，MKRN 3缺陷是家族性CPP最常见的已知遗传原因。在这篇综述中，我们探讨了临床，激素和遗传方面的儿童散发性或家族性CPP引起的突变kisspeptin和MKRN 3系统，青春期时间的基本遗传因素。(C)2014 S. Karger AG，巴塞尔
A pivotal event in the onset of puberty in humans is the reemergence of the pulsatile release of the gonadotropin-releasing hormone (GnRH) from hypothalamic neurons. Pathways governing GnRH ontogeny and physiology have been discovered by studying animal models and humans with reproductive disorders. Recent human studies implicated the activation of kisspeptin and its cognate receptor (KISS1 / KISS1R) and the inactivation of MKRN3 in the premature reactivation of GnRH secretion, causing central precocious puberty (CPP). MKRN3, an imprinted gene located on the long arm of chromosome 15, encodes makorin ring finger protein 3, which is involved in ubiquitination and cell signaling. The MKRN3 protein is derived only from RNA transcribed from the paternally inherited copy of the gene due to maternal imprinting. Currently, MKRN3 defects represent the most frequent known genetic cause of familial CPP. In this review, we explored the clinical, hormonal and genetic aspects of children with sporadic or familial CPP caused by mutations in the kisspeptin and MKRN3 systems, essential genetic factors for pubertal timing. (C) 2014 S. Karger AG, Basel