Examination of reproductive aging milestones among women who carry the FMRI premutation
Examination of reproductive aging milestones among women who carry the FMRI premutation
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DOI：
10.1093/humrep/dem148
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发表时间：
2007-08-01
影响因子：
6.1
通讯作者：
Sherman, S. L.
中科院分区：
文献类型：
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作者：
Allen, E. G.;Sullivan, A. K.;Sherman, S. L.
背景：脆性X基因前突变的特征是FMR 1基因5'非翻译区有一个大的CGG重复序列（55-199个重复）。这种X连锁突变导致卵巢早衰的风险增加;有趣的是，重复序列大小与风险的关联是非线性的。我们假设，前突变相关的卵巢功能不全是由于减少卵母细胞池和检查生殖年龄的里程碑重复大小组，以确定是否相同的非线性associationsobserved.METHODS：我们分析了横断面生殖史问卷调查数据，从948名妇女与广泛的重复大小。中等重复组（80-100个重复），而不是最高的组，有一个增加的风险：改变周期特征（缩短周期长度，不规则的周期和跳过周期），低生育力和双卵双胞胎。吸烟，一种可改变的风险，减少了大约1年的前突变妇女的生殖寿命，类似于其对非携带者的影响。正如预期的那样，前突变携带者被发现是在一个增加的风险为osteoporosis.CONCLUSIONS：可能的分子机制来解释卵巢功能不全的非线性重复大小的风险进行了讨论。
BACKGROUND: The fragile X premutation is characterized by a large CGG repeat track (55-199 repeats) in the 5' UTR of the FMR1 gene. This X-linked mutation leads to an increased risk for premature ovarian failure; interestingly, the association of repeat size with risk is non-linear. We hypothesize that the premutation-associated ovarian insufficiency is due to a diminished oocyte pool and examined reproductive aging milestones by repeat size group to determine if the same non-linear association is observed.METHODS: We analyzed cross-sectional reproductive history questionnaire data from 948 women with a wide range of repeat sizes.RESULTS: We have confirmed the nonlinear relationship among premutation carriers for ovarian insufficiency. The mid-range repeat size group (80-100 repeats), not the highest group, had an increased risk for: altered cycle traits (shortened cycle length, irregular cycles and skipped cycles), subfertility and dizygotic twinning. Smoking, a modifiable risk, decreased the reproductive lifespan of women with the premutation by about 1 year, similar to its effect on non-carriers. As expected, premutation carriers were found to be at an increased risk for osteoporosis.CONCLUSIONS: Possible molecular mechanisms to explain the non-linear repeat size risk for ovarian insufficiency are discussed.