Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort
Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort
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DOI：
10.1002/ajmg.a.30617
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发表时间：
2005-04-30
影响因子：
2
通讯作者：
Flanigan, KM
中科院分区：
文献类型：
--
作者：
Dent, KM;Dunn, DM;Flanigan, KM
DMD基因突变导致杜氏肌营养不良症（DMD）和贝克肌营养不良症（BMD）。现有的临床检测仅检测到一个或更多外显子的缺失，这在大约60%的病例中发现。其他类型的DMD突变的突变分析，如过早的终止密码子和小的移码插入或缺失，历来受到基因大小的阻碍。我们最近报道了一种方法，它允许快速和经济的DMD基因的整个编码区的测序，这是更敏感的方法比基于单链构象。多态性（SSCP）筛选或其他初步筛选步骤。在这里，我们使用单一条件扩增/内部引物（SCAIP）测序分析，结合多重可扩增探针杂交（MAPH）分析的重复，报告突变的频率在一个大队列的肌营养不良蛋白病患者从一个单一的诊所。我们的研究结果表明，7%的肌营养不良蛋白病患者没有编码区突变，这表明内含子突变并不罕见。外周血样本的快速和彻底的突变分析的可用性，沿着非编码区突变百分比的改进估计，将有利于改进遗传咨询和临床试验队列的识别。(c)2005年威利-利斯。
Mutations in the DMD gene result in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Readily available clinical tests detect only deletions of one exon or greater, which are found in approximately 60% of cases. Mutational analysis of other types of DMD mutations, such as premature stop codons and small frame-shifting insertions or deletions, has historically been hampered by the large size of the gene. We have recently reported a method that allows the rapid and economical sequencing of the entire coding region of the DMD gene, and that is more sensitive than methods based on single-strand conformational. polymorphism (SSCP) screening or other preliminary screening steps. Here we use single condition amplification/internal primer (SCAIP) sequencing analysis, in combination with multiplex amplifiable probe hybridization (MAPH) analysis of duplications, to report the frequency of mutations in a large cohort of unselected dystrophinopathy patients from a single clinic. Our results indicate that 7% of dystrophinopathy patients do not have coding region mutations, suggesting that intronic mutations are not uncommon. The availability of rapid and thorough mutation analysis from peripheral blood samples, along with an improved estimate of the percentage of non-coding region mutations, will be of benefit for improved genetic counseling and in identification of cohorts for clinical trials. (c) 2005 Wiley-Liss.