PDF(Pubmed)
Abstract：
Gonadal development is the first step in human reproduction. Aberrant gonadal development during the fetal period is a major cause of disorders/differences of sex development (DSD). To date, pathogenic variants of three nuclear receptor genes (NR5A1, NR0B1, and NR2F2) have been reported to cause DSD via atypical testicular development. In this review article, we describe the clinical significance of the NR5A1 variants as the cause of DSD and introduce novel findings from recent studies. NR5A1 variants are associated with 46,XY DSD and 46,XX testicular/ovotesticular DSD. Notably, both 46,XX DSD and 46,XY DSD caused by the NR5A1 variants show remarkable phenotypic variability, to which digenic/oligogenic inheritances potentially contribute. Additionally, we discuss the roles of NR0B1 and NR2F2 in the etiology of DSD. NR0B1 acts as an anti-testicular gene. Duplications containing NR0B1 result in 46,XY DSD, whereas deletions encompassing NR0B1 can underlie 46,XX testicular/ovotesticular DSD. NR2F2 has recently been reported as a causative gene for 46,XX testicular/ovotesticular DSD and possibly for 46,XY DSD, although the role of NR2F2 in gonadal development is unclear. The knowledge about these three nuclear receptors provides novel insights into the molecular networks involved in the gonadal development in human fetuses.
摘要：
性腺发育是人类生殖的第一步。胎儿期的异常性腺发育是性发育障碍/差异（DSD）的主要原因。迄今为止,据报道,三种核受体基因(NR5A1,NR0B1和NR2F2)的致病变异体可通过非典型睾丸发育引起DSD.在这篇评论文章中，我们描述了NR5A1变异体作为DSD病因的临床意义,并介绍了近期研究的新发现.NR5A1变体与46，XYDSD和46，XX睾丸/睾丸DSD相关。值得注意的是,由NR5A1变体引起的46，XXDSD和46，XYDSD均显示出显着的表型变异性，双基因/寡基因遗传可能对其做出贡献。此外,我们讨论了NR0B1和NR2F2在DSD病因中的作用。NR0B1充当抗睾丸基因。包含NR0B1的副本导致46，XYDSD，而包含NR0B1的缺失可以作为46，XX睾丸/睾丸DSD的基础。NR2F2最近被报道为46，XX睾丸/睾丸DSD的致病基因，可能为46，XYDSD，尽管NR2F2在性腺发育中的作用尚不清楚。关于这三种核受体的知识为参与人类胎儿性腺发育的分子网络提供了新的见解。
