Array-Based FMR1 Sequencing and Deletion Analysis in Patients with a Fragile X Syndrome-Like Phenotype
Array-Based FMR1 Sequencing and Deletion Analysis in Patients with a Fragile X Syndrome-Like Phenotype
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DOI：
10.1371/journal.pone.0009476
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发表时间：
2010-03-05
期刊：
影响因子：
3.7
通讯作者：
Warren, Stephen T.
中科院分区：
文献类型：
--
作者：
Collins, Stephen C.;Coffee, Brad;Warren, Stephen T.
背景：脆性X综合征（FXS）是由FMR 1基因功能缺失突变引起的。三核苷酸CGG重复扩增，导致FMR 1基因沉默，是在该位点观察到的最常见的突变。尽管重复扩增突变是一种功能性无效突变，但在该基因座很少发现常规突变，这主要是由于临床实验室对重复序列的关注。方法学/主要发现：为了更彻底地评估FXS样患者中常规突变的频率，我们使用基于阵列的方法对51名表现出FXS特征但具有正常FMR 1 CGG重复序列的无关男性的FMR 1进行测序。一名患者被确定为FMR 1的缺失，但没有一个患者被发现有其他常规mutations.Conclusions/Significance：这些数据表明，错义突变FMR 1中的FXS表型的患者谁具有正常长度的CGG重复序列的一个共同的原因。然而，筛查FMR 1的小缺失可能具有临床实用性。
Background: Fragile X syndrome (FXS) is caused by loss of function mutations in the FMR1 gene. Trinucleotide CGG-repeat expansions, resulting in FMR1 gene silencing, are the most common mutations observed at this locus. Even though the repeat expansion mutation is a functional null mutation, few conventional mutations have been identified at this locus, largely due to the clinical laboratory focus on the repeat tract.Methodology/Principal Findings: To more thoroughly evaluate the frequency of conventional mutations in FXS-like patients, we used an array-based method to sequence FMR1 in 51 unrelated males exhibiting several features characteristic of FXS but with normal CGG-repeat tracts of FMR1. One patient was identified with a deletion in FMR1, but none of the patients were found to have other conventional mutations.Conclusions/Significance: These data suggest that missense mutations in FMR1 are not a common cause of the FXS phenotype in patients who have normal-length CGG-repeat tracts. However, screening for small deletions of FMR1 may be of clinically utility.