Chapman Chevy, Cree Lynsey, Shelling Andrew N
Department of Obstetrics and Gynecology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Int J Womens Health. 2015 Sep 23;7:799-810. doi: 10.2147/IJWH.S64024. eCollection 2015.
Premature ovarian failure (POF) is a common cause of infertility in women, characterized by amenorrhea, hypoestrogenism, and elevated gonadotropin levels in women under the age of 40. Many genes have been identified over the past few years that contribute to the development of POF. However, few genes have been identified that can explain a substantial proportion of cases of POF. The unbiased approaches of genome-wide association studies and next-generation sequencing technologies have identified several novel genes implicated in POF. As only a small proportion of genes influencing idiopathic POF have been identified thus far, it remains to be determined how many genes and molecular pathways may influence idiopathic POF development. However, owing to POF's diverse etiology and genetic heterogeneity, we expect to see the contribution of several new and novel molecular pathways that will greatly enhance our understanding of the regulation of ovarian function. Future genetic studies in large cohorts of well-defined, unrelated, idiopathic POF patients will provide a great opportunity to identify the missing heritability of idiopathic POF. The identification of several causative genes may allow for early detection and would provide better opportunity for early intervention, and furthermore, the identification of specific gene defects will help direct potential targets for future treatment.
卵巢早衰（POF）是女性不孕的常见原因，其特征为40岁以下女性出现闭经、雌激素缺乏和促性腺激素水平升高。在过去几年中，已经鉴定出许多与POF发生发展相关的基因。然而，能够解释相当比例POF病例的基因却很少。全基因组关联研究和下一代测序技术的无偏倚方法已经鉴定出几个与POF相关的新基因。由于迄今为止仅鉴定出一小部分影响特发性POF的基因，因此仍有待确定有多少基因和分子途径可能影响特发性POF的发展。然而，由于POF病因多样且遗传异质性高，我们预计会看到一些新的分子途径的作用，这将极大地增进我们对卵巢功能调节的理解。未来在大量明确诊断、无亲缘关系的特发性POF患者队列中进行的基因研究，将为确定特发性POF缺失的遗传度提供绝佳机会。鉴定出几个致病基因可能有助于早期检测，并为早期干预提供更好的机会，此外，鉴定特定的基因缺陷将有助于指导未来治疗的潜在靶点。
