Mechanisms of disease: Transcription factors in sex determination--relevance to human disorders of sex development.
Mechanisms of disease: Transcription factors in sex determination--relevance to human disorders of sex development.
复制标题
疾病机制：性别决定中的转录因子——与人类性发育障碍的相关性。
DOI：
10.1038/ncpendmet0143
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发表时间：
2006
影响因子：
--
通讯作者：
Vilain,Eric
中科院分区：
文献类型：
--
作者：
Nikolova,Ganka;Vilain,Eric
性别决定是指导未分化的双势性腺变成睾丸或卵巢的一系列分子事件。在人类中，这一过程的中断会导致中间性，也被称为性发育障碍（DSD）。尽管15年前发现了性别决定基因（性别决定区域Y），但性别决定的分子机制仍然知之甚少。对DSD患者中性别决定基因的临床相关突变的分析为这些基因的功能提供了相当大的见解。已知原因的大多数性别决定障碍可以通过性别决定途径核心的三个转录因子之一的突变来解释：SRY， SOX9 （SRY-box 9）和NR5A1（核受体亚家族5，A组，成员1）。这些突变要么影响其核作用位点的可用蛋白质水平（通过改变调控序列、缺失、无义突变或核定位序列突变），要么改变蛋白质的结构（通过改变结合或弯曲活性，或与其他蛋白质的相互作用）。破译影响性别决定通路的突变的功能多样性对DSD患者的诊断、结局研究和分类具有直接的临床影响。
Sex determination is the series of molecular events that direct the undifferentiated bipotential gonad to become either a testis or an ovary. In humans, disruption of this process results in intersexuality, also referred to as disorders of sex development (DSD). Despite the discovery of the sex-determining geneSRY(sex-determining region Y) 15 years ago, the molecular mechanisms of sex determination remain poorly understood. Analysis of clinically relevant mutations of sex-determining genes in individuals with DSD has provided considerable insight into the function of these genes. The majority of disorders of sex determination with known causes are explained by mutations in one of three transcription factors at the core of the sex-determining pathway: SRY, SOX9 (SRY-box 9) and NR5A1 (nuclear receptor subfamily 5, group A, member 1). These mutations either affect the level of protein available at its nuclear site of action (via changes in regulatory sequences, deletions, non-sense mutations or mutations in nuclear localization sequences), or alter the structure of the protein (via modifications of binding or bending activity, or of interactions with other proteins). Deciphering the functional diversity of the mutations affecting the sex-determining pathway has immediate clinical impact on the diagnosis, outcome studies and classification of patients with DSD.