Prevalence and instability of fragile X alleles - Implications for offering fragile X prenatal diagnosis
Prevalence and instability of fragile X alleles - Implications for offering fragile X prenatal diagnosis
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DOI：
10.1097/aog.0b013e318163be0b
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发表时间：
2008-03-01
影响因子：
7.2
通讯作者：
Hallam, Stephanie
中科院分区：
文献类型：
--
作者：
Cronister, Amy;Teicher, Jennifer;Hallam, Stephanie
目的：为了记录脆性X等位基因频率在全国转诊人群和评估CGG重复扩增在母婴transmiss.METHODS：脆性X DNA分析Southern印迹和聚合酶链反应完成了14,675名妇女，年龄在18岁或以上，和238个母亲和子女对1999年1月至2004年6月。比较了不同临床适应症组间的载波频率。直接比较FMR 1基因CGG重复序列大小的母子配对确定中间和前突变等位基因的稳定性。具有前突变（55 - 200个CGG重复）或完全突变（超过200个CGG重复）的患者的合并总数为208例（1/71）。有脆性X家族史的女性中，每3.5人中就有1人，卵巢早衰的女性中，每10人中就有1人有FMR 1突变。相比之下，在有精神发育迟滞家族史的女性中，这一比例为1/86，而在没有已知的脆性X危险因素的女性中，这一比例为1/257。在238对母子配对中，在一代中扩展到完全突变的最小等位基因包含60个CGG重复。虽然6.6%（460）的中间重复等位基因没有扩大，没有跳到一个临床上显着的完整的突变大小allele.CONCLUSION：根据这些数据和其他已发表的文献，提供侵入性产前诊断脆性X综合征是不适用于妇女与中间等位基因。对于携带脆性X等位基因且CGG重复数在55个以上的妇女，应进行有创性产前诊断。
OBJECTIVE: To document fragile X allele frequencies in a national referral population and evaluate CGG repeat expansion in mother-offspring transmissions.METHODS: Fragile X DNA analysis by Southern blot and polymerase chain reaction was completed for 14,675 women, aged 18 years or older, and 238 mother-offspring pairs between January 1999 and June 2004. Carrier frequencies were compared between groups referred for different clinical indications. Direct comparison of the FMR1 gene CGG repeat size in mother-offspring pairs determined intermediate and premutation allele stability.RESULTS: Intermediate fragile X alleles (45-54 CGG repeats) occurred in 257 (1 in 57). The combined total number of patients with a premutation (55-200 CGG repeats) or full mutation (more than 200 CGG repeats) numbered 208 (1 in 71). One in 3.5 women with a family history of fragile X and 1 in 10 with premature ovarian failure had a FMR1 mutation. This compared with 1 in 86 for those with a family history of mental retardation and 1 in 257 for women with no known risk factors for fragile X. Among 238 mother-offspring pairings, the smallest allele to expand to a full mutation in one generation contained 60 CGG repeats. Although 6.6% (4 of 60) of intermediate repeat alleles did expand, none jumped to a clinically significant full mutation-sized allele.CONCLUSION: Based on these data and other published literature, offering invasive prenatal diagnosis for fragile X syndrome is not indicated for women with intermediate alleles. Invasive prenatal diagnosis is warranted for those women with a fragile X allele containing 55 or more CGG repeats.