Man Limor, Lekovich Jovana, Rosenwaks Zev, Gerhardt Jeannine
The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell MedicineNew York, NY, United States.
Front Mol Neurosci. 2017 Sep 12;10:290. doi: 10.3389/fnmol.2017.00290. eCollection 2017.
Fragile X syndrome (FXS), is caused by a loss-of-function mutation in the gene located on the X-chromosome, which leads to the most common cause of inherited intellectual disability in males and the leading single-gene defect associated with autism. A full mutation (FM) is represented by more than 200 CGG repeats within the gene, resulting in FXS. A FM is inherited from women carrying a FM or a premutation (PM; 55-200 CGG repeats) allele. PM is associated with phenotypes distinct from those associated with FM. Some manifestations of the PM are unique; fragile-X-associated tremor/ataxia syndrome (FXTAS), and fragile-X-associated primary ovarian insufficiency (FXPOI), while others tend to be non-specific such as intellectual disability. In addition, women carrying a PM may suffer from subfertility or infertility. There is a need to elucidate whether the impairment of ovarian function found in PM carriers arises during the primordial germ cell (PGC) development stage, or due to a rapidly diminishing oocyte pool throughout life or even both. Due to the possibility of expansion into a FM in the next generation, and other ramifications, carrying a PM can have an enormous impact on one's life; therefore, preconception counseling for couples carrying the PM is of paramount importance. In this review, we will elaborate on the clinical manifestations in female PM carriers and propose the definition of fragile-X-associated diminished ovarian reserve (FXDOR), then we will review recent scientific findings regarding possible mechanisms leading to FXDOR and FXPOI. Lastly, we will discuss counseling, preventative measures and interventions available for women carrying a PM regarding different aspects of their reproductive life, fertility treatment, pregnancy, prenatal testing, contraception and fertility preservation options.
脆性X综合征（FXS）由位于X染色体上的基因功能丧失突变引起，是男性遗传性智力残疾的最常见原因，也是与自闭症相关的主要单基因缺陷。全突变（FM）由该基因内200多个CGG重复序列表示，导致脆性X综合征。FM从携带FM或前突变（PM；55 - 200个CGG重复序列）等位基因的女性遗传而来。PM与不同于FM的表型相关。PM的一些表现是独特的；脆性X相关震颤/共济失调综合征（FXTAS）和脆性X相关原发性卵巢功能不全（FXPOI），而其他表现往往是非特异性的，如智力残疾。此外，携带PM的女性可能会出现生育力低下或不育。有必要阐明在PM携带者中发现的卵巢功能损害是在原始生殖细胞（PGC）发育阶段出现的，还是由于一生中卵母细胞池迅速减少，甚至两者兼而有之。由于下一代有可能扩展为FM以及其他后果，携带PM会对一个人的生活产生巨大影响；因此，为携带PM的夫妇提供孕前咨询至关重要。在本综述中，我们将详细阐述女性PM携带者的临床表现，并提出脆性X相关卵巢储备减少（FXDOR）的定义，然后我们将回顾关于导致FXDOR和FXPOI的可能机制的最新科学发现。最后，我们将讨论针对携带PM的女性在其生殖生活、生育治疗、怀孕、产前检测、避孕和生育力保存选择等不同方面的咨询、预防措施和干预措施。
