Screening for Expanded Alleles of the FMR1 Gene in Blood Spots from Newborn Males in a Spanish Population
Screening for Expanded Alleles of the FMR1 Gene in Blood Spots from Newborn Males in a Spanish Population
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DOI：
10.2353/jmoldx.2009.080173
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发表时间：
2009-07-01
影响因子：
4.1
通讯作者：
Tassone, Flora
中科院分区：
文献类型：
--
作者：
Fernandez-Carvajal, Isabel;Walichiewicz, Paulina;Tassone, Flora
脆性X综合征是由FMR 1基因的CGG重复序列扩增引起的，与广泛的临床累及相关，是智力残疾最常见的遗传形式。早期诊断和干预可能会改善脆性X综合征儿童的预后，但这些策略需要更好地估计FMR 1基因扩增等位基因的频率。在这项研究中，我们报告的结果，新生儿筛查研究的5267名男性血液斑点收集从西班牙西北地区的国家新生儿筛查计划的一部分。使用基于快速聚合酶链反应的方法筛选血斑，该方法能够鉴定男性和女性所有扩增等位基因的存在。筛选的样本包括199个灰色区等位基因，21个前突变等位基因和2个全突变等位基因（1/2633）。前突变等位基因的频率是3倍高（I在251）比引用的值1在813从加拿大人口，是完全符合以色列的大规模筛选研究的结果。我们的研究结果表明，新生儿筛查扩展FMR 1等位基因的存在是一种有效的手段，用于定义扩展FMR 1等位基因在新生儿人群中的分布，因此，这种方法适用于大规模的新生儿筛查。（J Mol Diagn 2009，11：324-329; DOI：10.2353/jmoldx.2009.080173）
Fragile X syndrome, which is caused by expanded CGG repeats of the FMR1 gene, is associated with a broad spectrum of clinical involvement and is the most common inherited form of intellectual disability. Early diagnosis and intervention are likely to lead to improved outcome for children with fragile X syndrome, but such strategies require better estimates of the frequencies of expanded alleles of the FMR1 gene. In this study, we report the results of a newborn screening study of 5267 male blood spots collected from the Northwest region of Spain as part of the national newborn screening program. The blood spots were screened using a rapid polymerase chain reaction-based method that is capable of identifying the presence of all expanded alleles for both males and females. The screened samples included 199 gray zone alleles, 21 premutation alleles, and two full mutation alleles (1 in 2633). The frequency of premutation alleles was three times higher (I in 251) than the quoted value of 1 in 813 from a Canadian population and is fully consistent with the results of large-scale Israeli screening studies. Our results demonstrate that newborn screening for the presence of expanded FMR1 alleles is an effective means for defining the distribution of expanded FMR1 alleles in newborn populations; as such, this method is suitable for large-scale newborn screening. (J Mol Diagn 2009, 11:324-329; DOI:10.2353/jmoldx.2009.080173)