Romey M-C
Laboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Montpellier.
Ann Biol Clin (Paris). 2006 Sep-Oct;64(5):429-37.
Cystic fibrosis is caused by mutations in the CFTR gene (Cystic Fibrosis Transmembrane conductance Regulator) encodes a protein mainly functioning as a chloride channel that regulates chloride and sodium transport in secretory epithelial cells. The past several years with advances in DNA analysis have seen an increased knowledge of the mutational spectrum for cystic fibrosis. The functional characterization of some naturally occurring CFTR mutants led to classification of mutations according to the mechanisms by which they disrupt CFTR function. This article reports the strategies that are currently available to evaluate the deleterious consequences of naturally occurring CFTR mutants. A number of in silico tools and molecular approaches are presented. The accurate knowledge of CFTR mutations causing or non-causing disease present obvious interest in both clinical diagnosis and research fields. A better understanding of the molecular defects associated with various CFTR mutations will provide a basis for development of novel pharmacologic compounds intended to correct transcriptional abnormalities or improve protein processing/trafficking. This is illustrated by the functional characterization of the first sequence variation identified in the CFTR minimal promoter, which allowed to address in original way the important and poorly understood regulation of expression of the CFTR gene.
囊性纤维化由CFTR基因（囊性纤维化跨膜传导调节因子）突变引起，该基因编码一种主要作为氯离子通道的蛋白质，调节分泌性上皮细胞中的氯离子和钠离子运输。在过去几年中，随着DNA分析技术的进步，人们对囊性纤维化的突变谱有了更多了解。一些天然存在的CFTR突变体的功能特性导致根据它们破坏CFTR功能的机制对突变进行分类。本文报道了目前可用于评估天然存在的CFTR突变体有害后果的策略。介绍了一些计算机工具和分子方法。准确了解导致或不导致疾病的CFTR突变在临床诊断和研究领域都具有明显的意义。更好地理解与各种CFTR突变相关的分子缺陷将为开发旨在纠正转录异常或改善蛋白质加工/运输的新型药物化合物提供基础。CFTR最小启动子中鉴定出的第一个序列变异的功能特性就说明了这一点，它以原始方式解决了CFTR基因表达中重要但了解不足的调控问题。
