FMR1 premutation carrier frequency in patients undergoing routine population-based carrier screening: Insights into the prevalence of fragile X syndrome, fragile X-associated tremor/ataxia syndrome, and fragile X-associated primary ovarian insufficiency in the United States
FMR1 premutation carrier frequency in patients undergoing routine population-based carrier screening: Insights into the prevalence of fragile X syndrome, fragile X-associated tremor/ataxia syndrome, and fragile X-associated primary ovarian insufficiency in the United States
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DOI：
10.1097/gim.0b013e3181fa9fad
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发表时间：
2011-01-01
影响因子：
8.8
通讯作者：
Strom, Charles M.
中科院分区：
文献类型：
--
作者：
Hantash, Feras M.;Goos, Dana M.;Strom, Charles M.
目的：脆性X综合征是由FMR 1基因5'端非翻译区CGG序列的扩增和甲基化引起的。在美国，扩增等位基因（>= 55个重复）的估计频率为1：257-1：382，但这些估计值不是从无偏群体中计算出来的。我们试图确定脆性X综合征前突变（55-200个重复）和全突变（>200个重复）等位基因在非选择性、无偏倚人群中的频率，这些人群接受常规的其他疾病携带者筛查。研究方法：一个先前验证的实验室开发的测试使用三重引物聚合酶链反应被用来检测前突变和全突变等位基因在一个连续的11,759个囊性纤维化携带者筛查样本和2011年提交的遗传疾病筛查德系犹太人人口中流行的一个连续的系列。结果：在48份囊性纤维化筛查样本（1：245）和15份来自德系犹太人人群的样本（1：134）中确定了前突变。根据美国人群的种族混合和我们筛选人群中自我报告的种族进行调整，美国女性前突变携带者频率估计为1：178。全突变等位基因的计算频率总体为1：3335，男性中的前突变频率为1：400。根据大于等于70个重复等位基因的频率和报道的重复率，计算出脆性X相关震颤和共济失调综合征以及脆性X相关原发性卵巢功能不全的频率分别为1：4848和1：3560。结论：我们计算出的脆性X综合征携带率高于以前对美国人口的估计，并值得进一步考虑基于人口的携带者筛查。Genet Med 2011：13（1）：39-45.
Purpose: Fragile X syndrome is caused by expansion and methylation of a CGG tract in the 5' untranslated region of the FMR1 gene. The estimated frequency of expanded alleles (>= 55 repeats) in the United States is 1:257-1:382, but these estimates were not calculated from unbiased populations. We sought to determine the frequency of fragile X syndrome premutation (55-200 repeats) and full mutation (>200 repeats) alleles in nonselected, unbiased populations undergoing routine carrier screening for other diseases. Methods: A previously validated laboratory-developed test using triplet-primed polymerase chain reaction was used to detect premutation and full mutation alleles in an unselected series of 11,759 consecutive cystic fibrosis carrier screening samples and 2011 samples submitted for screening for genetic diseases prevalent among the Ashkenazi Jewish population. Results: Premutations were identified in 48 cystic fibrosis screening samples (1: 245) and 15 samples (1: 134) from the Ashkenazi Jewish population. Adjusted for the ethnic mix of the US population and self-reported ethnicity in our screening population, the estimated female premutation carrier frequency in the United States was 1:178. The calculated frequency of full mutation alleles was 1: 3335 overall, and the calculated premutation frequency in males was 1:400. Based on frequency of larger, >= 70 repeat alleles, and reported penetrance, the calculated fragile X-associated tremor and ataxia syndrome, and fragile X-associated primary ovarian insufficiency frequencies is 1: 4848 and 1: 3560, respectively. Conclusion: Our calculated fragile X syndrome carrier rate is higher than previous estimates for the US population and warrants further consideration of population-based carrier screening. Genet Med 2011:13(1):39-45.