Genetic and phenotypic heterogeneity in ovarian failure - Overview of selected candidate genes
Genetic and phenotypic heterogeneity in ovarian failure - Overview of selected candidate genes
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DOI：
10.1196/annals.1429.019
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发表时间：
2008-01-01
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影响因子：
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通讯作者：
Simpson, Joe Leigh
中科院分区：
文献类型：
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作者：
Simpson, Joe Leigh
卵巢衰竭在病因和表型上都是异质性的。临床医生传统上认为，月经在40岁之前停止并有绝经期FSH水平的女性被诊断为“卵巢早衰”(POF)。然而，事实上，这种疾病的卵巢功能实际上是卵巢反应性的一系列损害。出于这个原因，术语“原发性卵巢功能不全”(POI)被认为更准确。根据异常的胚胎分化而不是卵巢功能状态来对这种疾病进行分类是更可取的。已知的激素效应基因(FSH、FSHR、LH、LHR、CYP17、CYP19)主要影响卵泡功能，BMP15、GDF9和GPR3也是如此。这些基因突变偶尔会在人类身上发现，但没有一个是常见的。然而，在卵子发生过程中表达的其他基因似乎更有可能以缺乏生殖细胞形成为特征。这些包括DNA结合蛋白和转录因子，如NOBOX和LHX8，以及RNA结合蛋白，如Nanos。在少数女性(NOBOX、GDF9、LDX8)中发现了看似合理的致病突变，但即使这样，也只有1%-2%的病例表现出扰动。因此，无论卵泡是否发育，卵巢衰竭都存在相当大的异质性--表型和病因。对其他基因的分析是必要的，包括许多可能显示新的作用机制的基因。
Ovarian failure is heterogeneous, both in cause and in phenotype. Women whose menses cease prior to age 40 years and have menopausal FSH levels are traditionally considered by clinicians to have the diagnosis of "premature ovarian failure" (POF). In fact, however, the ovarian function in this disorder is in reality a continuum of impairment in ovarian responsiveness. For this reason the term "primary ovarian insufficiency" (POI) has been suggested to be more accurate. It would be yet more desirable to classify this disorder on the basis of aberrant embryonic differentiation rather than the state of ovarian function. Genes that exert known hormonal effects (FSH, FSHR, LH, LHR, CYP17, CYP19) primarily affect follicle function, as do BMP15, GDF9, and GPR3. These genes mutations have occasionally been found in humans, but none are common. Still other genes expressed during oogenesis appear more likely to be characterized by lack of germ cell formation. These include DNA binding proteins and transcription factors like NOBOX and LHX8, and RNA binding proteins like NANOS. Plausible causative mutations have been identified in a few women (NOBOX, GDF9, LDX8), but even then only 1-2% of cases show a perturbation. Thus, considerable heterogeneity-phenotypic as well as etiologic-exists in ovarian failure, irrespective of whether follicles do or do not develop. Analysis of other genes is necessary, including many likely to show novel mechanisms of action.