Epidemiology and a novel procedure for large scale analysis of CFTR rearrangements in classic and atypical CF patients: A multicentric Italian study
Epidemiology and a novel procedure for large scale analysis of CFTR rearrangements in classic and atypical CF patients: A multicentric Italian study
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DOI：
10.1016/j.jcf.2007.12.004
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发表时间：
2008-09-01
影响因子：
5.2
通讯作者：
Novelli, G.
中科院分区：
文献类型：
--
作者：
Tomaiuolo, R.;Sangiuolo, F.;Novelli, G.
背景：各种族人群的突变流行病学是囊性纤维化（CF）诊断和咨询策略的关键步骤。到目前为止，囊性纤维化跨膜传导调节因子（CFTR）基因的整个编码区的扫描允许识别约90%的等位基因从携带CF的患者和携带非典型CF的患者的百分比较低。CFTR重排在杂合子逃避目前的分子分析技术，其中一些已报道的频率高达6%，）在不同的种族群体。方法：使用所有编码区的定量PCR分析，我们评估了典型CF患者的130个等位基因和非典型CF患者的198个等位基因中CFTR重排的发生率（都是无关的并且来自意大利血统），在CFTR扫描后携带未鉴定的突变。结果：7个重排（即，dele 1、dele 2、dele 2 -3、dele 14 b-17 b、dele 17 a-18、dele22_23和dele 22 -24）在34/131（26.0%）携带未检测到突变的CF等位基因（这意味着约占所有CF等位基因的2.5%）中被鉴定，而在来自非典型CF的198个等位基因中没有一个被鉴定。CFTR。单倍型和断裂点的序列分析证实了所有重排的共同起源。因此，我们建立了一种新的双重PCR检测的大规模分析的七个重排。该程序是快速的（所有的PCR扩增在相同的条件下获得），成本低，repeated.Conclusions：这是有用的选择CFTR重排更频繁的特定种族群体和设置唇程序进行大规模的分析。他们的研究可以在需要高检测率的情况下进行（即，CF携带者/患者的伴侣）。相反，重排的分析是无用的，在不典型的CF患者。(C)2007年欧洲囊性纤维化协会。Elsevier B. V.出版，保留所有权利。
Background: Mutation epidemiology in each ethnic group is a crucial step of strategies for cystic fibrosis (CF) diagnosis and counselling. To date, the scanning of the whole coding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene permits to identify about 90% of alleles from patients bearing CF and a lower percentage in patients bearing atypical CF. CFTR rearrangements in heterozygosis elude current techniques for molecular analysis, and some of them have been reported with a frequency up to 6%,) in various ethnic groups.Methods: Using quantitative PCR analysis of all coding regions, we assessed the Occurrence of CFTR rearrangements in 130 alleles from classic CF patients and in 198 alleles from atypical CF patients (all unrelated and from Italian descent) bearing unidentified Mutations after the scanning of CFTR.Results: Seven rearrangements (i.e., dele1, dele2, dele2-3, dele 14b-17b, dele17a-18, dele22_23, and dele22-24) were identified in 34/131 (26.0%) CF alleles bearing undetected mutations (which means about 2.5% of all CF alleles) and in none of the 198 alleles from atypical CF. The CFTR. haplotype and the sequence analysis of the breakpoints confirmed the common origin of all the rearrangements. Thus, we set up a novel duplex PCR assay for the large-scale analysis of the seven rearrangements. The procedure was rapid (all PCR amplifications were obtained under the same conditions), costless and repeatable.Conclusions: It is useful to select the CFTR rearrangements more frequent in specific ethnic groups and to set Lip procedures for large-scale analysis. Their study can be performed in cases in which a high detection rate is required (i.e., partners of CF carriers/patients). On the contrary, the analysis of rearrangement is useless in atypical CF patients. (C) 2007 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.