Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Genet Med. 2011 Jul;13(7):643-50. doi: 10.1097/GIM.0b013e31821705e5.
Women who carry a fragile X mental retardation 1 premutation are at risk for fragile X-associated primary ovarian insufficiency and should be counseled for a potentially reduced fertility. Multiple factors can affect the age of onset and severity of fragile X-associated primary ovarian insufficiency. In this study, we assessed the predictive power of several factors with menopausal age, a surrogate measure of onset of fragile X-associated primary ovarian insufficiency.
Genetic, environmental, and reproductive factors were analyzed by Cox proportional hazard models in 1068 women, 385 of fragile X families ascertained through the Nijmegen study and 683 of fragile X families or general population families ascertained through the Atlanta study.
The highest association with menopausal age among fragile X mental retardation 1 premutation carriers was found for risk index by CGG repeat size (hazard ratio, 1.43) and smoking (hazard ratio, 1.34). Women from the Nijmegen cohort showed an overall lower age at menopause onset, for which a correction was made. A prediction model based on these two parameters, mean menopausal age of first-degree relatives with the same mutation status and the correction for ascertainment site, estimated the probability of becoming postmenopausal for premutation carriers, with a margin of 7-10%.
We conclude that this model serves as a first step toward clinical application of fragile X-associated primary ovarian insufficiency prediction.
携带脆性 X 智力低下 1 前突变的女性有发生脆性 X 相关原发性卵巢功能不全的风险，应告知其生育能力可能降低。多种因素可影响脆性 X 相关原发性卵巢功能不全的发病年龄和严重程度。本研究通过 Cox 比例风险模型评估了几个因素对绝经年龄的预测能力，绝经年龄是脆性 X 相关原发性卵巢功能不全发病的替代指标。
对 1068 名女性进行遗传、环境和生殖因素分析，其中 385 名来自通过尼美根研究确定的脆性 X 家族，683 名来自通过亚特兰大研究确定的脆性 X 家族或一般人群家族。
脆性 X 智力低下 1 前突变携带者中，与绝经年龄相关性最高的是 CGG 重复大小的风险指数（危险比，1.43）和吸烟（危险比，1.34）。尼美根队列的女性整体绝经年龄较低，对此进行了校正。基于这两个参数（具有相同突变状态的一级亲属的平均绝经年龄和对确定地点的校正）的预测模型估计了前突变携带者绝经的概率，偏差为 7-10%。
我们得出的结论是，该模型是脆性 X 相关原发性卵巢功能不全预测的临床应用的第一步。
