El-Seedy A, Pasquet M C, Shafiek H, Morsi T, Kitzis A, Ladevèze V
Department of Genetics, Alexandria University, Aflaton St., EL-Shatby-21545, Alexandria, Egypt.
Centre Hospitalier Universitaire (CHU) de Poitiers, Poitiers, France.
Cell Mol Biol (Noisy-le-grand). 2016 Nov 30;62(13):21-28. doi: 10.14715/cmb/2016.62.13.5.
Cystic fibrosis (CF) occurrence in Arab populations is not common and still remains underidentified. Furthermore, the lack of disease awareness and diagnosis facilities have mislead the identification of cystic fibrosis for decades. The knowledge about cystic fibrosis (CF) in Egypt is very limited, and a few reports have drawn attention to the existence of CF or CFTR-related disorders (CFTR-RDs) in the Egyptian population. Therefore a comprehensive genetic analysis of the CFTR gene was realized in patients of North Egypt. DNA samples of 56 Egyptian patients were screened for the CFTR gene mutations. The 27 exons and their flanking regions of the CFTR gene were amplified by PCR, using the published primer pairs, and were studied by automated direct DNA sequencing to detect disease-causing mutations. Moreover, large duplication/deletion was analysed by MLPA technique. CFTR screening revealed the identification of thirteen mutations including four novel ones: c.92G>A (p.Arg31His), c.2782G>C (p.Ala928Pro), c.3718-24G>A, c.4207A>G (p.Arg1403Gly) and nine previously reported mutations: c.454A>T (p.Met152Leu), c.902A>G (p.Tyr301Cys), c.1418delG, c.2620-15C>G, c.2997_3000delAATT, c.3154T>G (p.Phe1052Val), c.3872A>G (p.Gln1291Arg), c.3877G>A (p.Val1293Ile), c.4242+10T>C. Furthermore, eight polymorphisms were found: c.743+40A>G, c.869+11C>T, c.1408A>G, c.1584G>A, c.2562T>G, c.3870A>G, c.4272C>T, c.4389G>A. These mutations and polymorphisms were not previously described in the Egyptian population except for the c.1408A>G polymorphism. Here we demonstrate the importance of the newly discovered mutations in Egyptian patients and the presence of CF, whereas the p.Phe508del mutation is not detected. The identification of CFTR mutations will become increasingly important in undocumented populations. The current findings will help us expand the mutational spectrum of CF and establish the first panel of the CFTR gene mutations in the Egyptian population and design an appropriate strategy for future genetic diagnosis of CF.
囊性纤维化（CF）在阿拉伯人群中并不常见，且仍未得到充分识别。此外，疾病认知的缺乏和诊断设施的不足导致囊性纤维化的识别被误导了数十年。埃及关于囊性纤维化（CF）的知识非常有限，仅有少数报告关注到埃及人群中CF或CFTR相关疾病（CFTR-RDs）的存在。因此，对埃及北部患者进行了CFTR基因的全面遗传分析。对56名埃及患者的DNA样本进行CFTR基因突变筛查。使用已发表的引物对，通过聚合酶链反应（PCR）扩增CFTR基因的27个外显子及其侧翼区域，并通过自动直接DNA测序进行研究以检测致病突变。此外，采用多重连接探针扩增（MLPA）技术分析大片段重复/缺失。CFTR筛查发现了13种突变，包括4种新突变：c.92G>A（p.Arg31His）、c.2782G>C（p.Ala928Pro）、c.3718-24G>A、c.4207A>G（p.Arg1403Gly），以及9种先前报道的突变：c.454A>T（p.Met152Leu）、c.902A>G（p.Tyr301Cys）、c.1418delG、c.2620-15C>G、c.2997_3000delAATT、c.3154T>G（p.Phe1052Val）、c.3872A>G（p.Gln1291Arg）、c.3877G>A（p.Val1293Ile）、c.4242+10T>C。此外，还发现了8种多态性：c.743+40A>G、c.869+11C>T、c.1408A>G、c.1584G>A、c.2562T>G、c.3870A>G、c.4272C>T、c.4389G>A。除了c.1408A>G多态性外，这些突变和多态性此前在埃及人群中均未被描述。在此，我们证明了新发现的突变在埃及患者中的重要性以及CF的存在，而未检测到p.Phe508del突变。CFTR突变的识别在未记录人群中将变得越来越重要。目前的研究结果将有助于我们扩大CF的突变谱，建立埃及人群中CFTR基因突变的首个面板，并为未来CF的基因诊断设计合适的策略。
