PDF(Pubmed)
Abstract：
BACKGROUND: Premutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene, defined as between 55 and 200 CGGs, have been implicated in fragile X-associated primary ovarian insufficiency (FXPOI). Only 20% of female premutation carriers develop early ovulatory dysfunction, the reason for this incomplete penetrance is unknown. This study validated the mathematical model in premutation alleles, after assigning each allele a score representing allelic complexity. Subsequently, allelic scores were used to investigate the impact of allele complexity on age at amenorrhea for 58 premutation cases (116 alleles) previously published.
METHODS: The allelic score was determined using a formula previously described by our group. The impact of each allelic score on age at amenorrhea was analyzed using Pearson\'s test and a contour plot generated to visualize the effect.
RESULTS: Correlation of allelic score revealed two distinct complexity behaviors in premutation alleles. No significant correlation was observed between the allelic score of premutation alleles and age at amenorrhea. The same lack of significant correlation was observed regarding normal-sized alleles, despite a nearly significant trend.
CONCLUSIONS: Our results suggest that the use of allelic scores combination have the potential to explain female infertility, namely the development of FXPOI, or ovarian dysfunction, despite the lack of correlation with age at amenorrhea. Such a finding is of great clinical significance for early identification of females at risk of ovulatory dysfunction, enhancement of fertility preservation techniques, and increasing the probability for a successful pregnancy in females with premutations. Additional investigation is necessary to validate this hypothesis.
METHODS: The allelic score was determined using a formula previously described by our group. The impact of each allelic score on age at amenorrhea was analyzed using Pearson\'s test and a contour plot generated to visualize the effect.
RESULTS: Correlation of allelic score revealed two distinct complexity behaviors in premutation alleles. No significant correlation was observed between the allelic score of premutation alleles and age at amenorrhea. The same lack of significant correlation was observed regarding normal-sized alleles, despite a nearly significant trend.
CONCLUSIONS: Our results suggest that the use of allelic scores combination have the potential to explain female infertility, namely the development of FXPOI, or ovarian dysfunction, despite the lack of correlation with age at amenorrhea. Such a finding is of great clinical significance for early identification of females at risk of ovulatory dysfunction, enhancement of fertility preservation techniques, and increasing the probability for a successful pregnancy in females with premutations. Additional investigation is necessary to validate this hypothesis.
摘要：
背景：脆性X信使核糖核蛋白1（FMR1）基因的前突变，定义为55和200CGG之间，与脆性X相关的原发性卵巢功能不全（FXPOI）有关。只有20%的女性前突变携带者出现早期排卵功能障碍,这种不完整的外显率的原因是未知的。本研究在前突变等位基因中验证了数学模型，在分配每个等位基因后，一个代表等位基因复杂性的分数。随后，等位基因评分用于调查先前发表的58例前突变病例(116个等位基因)的等位基因复杂性对闭经时年龄的影响.
方法：使用我们组先前描述的公式确定等位基因评分。使用Pearson检验分析每个等位基因评分对闭经年龄的影响，并生成等高线图以可视化效果。
结果：等位基因评分的相关性揭示了前突变等位基因中两种不同的复杂性行为。在闭经时，前突变等位基因的等位基因评分与年龄之间没有显着相关性。关于正常大小的等位基因，观察到同样缺乏显著的相关性，尽管有一个几乎显著的趋势。
结论：我们的结果表明，等位基因评分组合的使用有可能解释女性不孕症，即FXPOI的发展，或卵巢功能障碍,尽管闭经与年龄缺乏相关性。这一发现对于早期识别有排卵障碍风险的女性具有重要的临床意义。加强生育力保存技术，并增加具有前突变的女性成功怀孕的可能性。额外的调查是必要的，以验证这一假设。
方法：使用我们组先前描述的公式确定等位基因评分。使用Pearson检验分析每个等位基因评分对闭经年龄的影响，并生成等高线图以可视化效果。
结果：等位基因评分的相关性揭示了前突变等位基因中两种不同的复杂性行为。在闭经时，前突变等位基因的等位基因评分与年龄之间没有显着相关性。关于正常大小的等位基因，观察到同样缺乏显著的相关性，尽管有一个几乎显著的趋势。
结论：我们的结果表明，等位基因评分组合的使用有可能解释女性不孕症，即FXPOI的发展，或卵巢功能障碍,尽管闭经与年龄缺乏相关性。这一发现对于早期识别有排卵障碍风险的女性具有重要的临床意义。加强生育力保存技术，并增加具有前突变的女性成功怀孕的可能性。额外的调查是必要的，以验证这一假设。
