Premature ovarian insufficiency – the need for a genomic map

Abstract

Premature ovarian insufficiency (POI) is a life-long disorder of heterogeneous etiology, presenting as adolescent primary amenorrhea in its most severe form, with an overall incidence of 1%. Idiopathic POI accounts for up to 70% of women with POI; and genomic, genetic, epidemiological, familial and cohort studies demonstrate a genetic component to this condition. Currently, the only genetic tests routinely performed in non-syndromic POI are FMR1 premutation and cytogenetics, the latter specifically for X-chromosome abnormalities. However, a myriad of genetic aberrations has been identified and implicated, some of which act in a monogenic Mendelian fashion. The presence of multiple genetic aberrations and the complexity of POI genomics are hardly surprising since the embryological formation of the primordial oocyte pool, postnatal oogenesis and folliculogenesis are all highly complex pathways. With this review, the aim is to discuss the current genetic etiologies in the emerging field of POI genomics. Promising candidate genes include STAG3, SYCE1, FIGLA, NOBOX, FSHR, BMP15 and INHA. This area has the potential to progress rapidly in light of advances in genomic technologies. The development of a POI genomic map not only will assist in understanding the underlying molecular mechanisms affecting ovarian function but will also be essential in designing predictive and diagnostic gene panels as well as future novel therapeutic strategies.

早发性卵巢功能不全 - 基因组图谱的需求 摘要

早发性卵巢功能不全(POI)是一种不同病因的终生疾病, 最严重的形式表现为青春期原发性闭经, 总发病率为1%。特发性POI占女性POI的70%；基因组、遗传学、流行病学、家族性和队列研究表明这是一种遗传因素。目前, 在非综合征性POI中常规进行的基因检测只有FMR1前突变和细胞遗传学, 后者专门针对X染色体异常。然而, 大量的遗传异常已经被识别和关联, 其中一些是单基因孟德尔式的作用。由于原始卵母细胞池的胚胎学形成、出生后卵子发生和卵泡发生都是高度复杂的途径, 因此多个遗传异常的存在和POI基因组学的复杂性并不令人惊讶。通过这篇综述, 目的是讨论当前POI基因组学新兴领域的遗传病因。可能的候选基因包括STAG3、SYCE1、FIGLA、NOBOX、FSHR、BMP15和INHA。鉴于基因组技术的进步, 这一领域有可能迅速发展。POI基因组图谱的开发不仅有助于理解影响卵巢功能的潜在分子机制, 而且对于设计预测性和诊断性基因芯片以及未来新的治疗策略也是必不可少的。

Keywords:

• Premature ovarian insufficiency
• genomics
• genetics

Acknowledgements

The authors would like to thank Prof. Catherine Williamson and Deborah Holloway for their support. They also thank Rosetree Trust and Kings Health Partners for funding.

Potential conflict of interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Kings Health Partners [R160803]; Rosetree Trust [A1140].