Denaturing high‐performance liquid chromatography (DHPLC)‐based prenatal diagnosis for tuberous sclerosis
Denaturing high‐performance liquid chromatography (DHPLC)‐based prenatal diagnosis for tuberous sclerosis
复制标题
基于变性高效液相色谱 (DHPLC) 的结节性硬化症产前诊断
作者：
P. Bénit;J. Bonnefont;Ali Kara Mostefa;C. Francannet;A. Munnich;P. Ray
结节性硬化症 (TSC) 是一种常见的常染色体显性遗传疾病（影响六千分之一的个体），由错构蛋白 (TSC1) 或马铃薯蛋白基因 (TSC2) 的各种突变引起。这种等位基因和非等位基因异质性使得遗传咨询和产前诊断变得困难，特别是因为很大一部分 TSC 病例是由新生突变引起的。因此，为了准确的咨询，必须识别引起疾病的突变，但目前的突变检测方法，如单链构象多态性（SSCP）或变性梯度凝胶电泳（DGGE）是劳动密集型的，检测效率有限。变性高效液相色谱 (DHPLC) 是一种高通量、半自动突变检测系统，据报道，对于高达 800bp 的 PCR 片段，突变检测率接近 100%。我们使用最近描述的 DHPLC 测定法，可以有效检测 TSC1 突变，分析从绒毛膜绒毛样本中提取的 DNA，以便对 TSC 进行产前诊断。发现胎儿没有遗传有害突变，并且通过单倍型分析证实了 DHPLC 诊断。这是第一个基于 DHPLC 的遗传病产前诊断。版权所有 © 2001 约翰·威利父子有限公司
Tuberous sclerosis (TSC) is a frequent autosomal‐dominant condition (affecting 1 in 6000 individuals) caused by various mutations in either the hamartin (TSC1) or the tuberin gene (TSC2). This allelic and non‐allelic heterogeneity makes genetic counseling and prenatal diagnosis difficult, especially as a significant proportion of TSC cases are due to de novo mutations. For this reason the identification of the disease causing mutation is mandatory for accurate counseling, yet current mutation detection methods such as single‐strand conformation polymorphism (SSCP) or denaturing gradient gel electrophoresis (DGGE) are labor intensive with limited detection efficiency. Denaturing high‐performance liquid chromatography (DHPLC) is a high‐throughput, semi‐automated mutation detection system with a reported mutation detection rate close to 100% for PCR fragments of up to 800 bp. We used a recently described DHPLC assay allowing the efficient detection of mutations in TSC1 to analyze the DNA extracted from a chorion villus sample in order to perform a prenatal diagnosis for TSC. The fetus was found not to have inherited the deleterious mutation and the DHPLC diagnosis was confirmed by haplotype analysis. This represents the first DHPLC‐based prenatal diagnosis of a genetic disease. Copyright © 2001 John Wiley & Sons, Ltd.
ABL 和 D9S114 之间的人 9q34.1 的 5.4 Mb 连续脉冲场凝胶电泳图，包括结节性硬化症 (TSC1) 区域。
DOI：
10.1006/geno.1995.1113
发表时间：
1995
期刊：
Genomics.
影响因子：
--
作者：
Henske,EP;Kwiatkowski,DJ
通讯作者：
Kwiatkowski,DJ
影响因子：
14.9
作者：
Liu, WG;Smith, DI;James, CD
通讯作者：
James, CD