Department of Medical Genetics, Kayseri Training and Research Hospital, Kayseri, Turkey.
Division of Pediatric Pulmonology, Department of Pediatrics, Erciyes University, Kayseri, Turkey.
Balkan Med J. 2021 Nov;38(6):357-364. doi: 10.5152/balkanmedj.2021.21199.
Cystic fibrosis, a pulmonary disease which is an autosomal recessive, inherited, multisystemic genetic disease commonly seen in the Caucasian race, is the most frequent cause of mortality and morbidity. So far, more than 2000 disease-causing gene variants have been found and this number has been increasing with the studies conducted. Although there is not yet enough data that include the Turkish population, the recent increase of studies is noteworthy.
To discover the genetic variation in patients diagnosed with cystic fibrosis in the Central Anatolian region.
Cross-sectional study.
The study was carried out in the Central Anatolian region in 3 pediatric pulmonology departments (Kayseri, Konya, and Ankara) in Turkey between July 2014 and December 2017. The Sanger and Next Generation Sequence analyses were used for exon and exon-intron boundaries in the cystic fibrosis transmembrane conductance regulatory (CFTR) gene, and in selected patients, mutation analysis was performed using the Multiplex Ligation-dependent Probe Amplification technique for large deletions and duplications.
CFTR gene analysis was performed for 316 patients and 215 of them were genetically diagnosed with cystic fibrosis. Sixtythree different variants were defined in these patients and 7 of these were large deletions/duplications detected with the MLPA method. The most frequent variants were F508del (29.6%), G85E (8.2%), N1303K (8.2%), Y515* (7.5%), and G542* (3.4%).
Using sequencing and Multiplex Ligation-dependent Probe Amplification methods, the identification of seven new mutations that were not previously reported in the literature contributes to a better understanding of the heterogeneous nature of CFTR mutations in the Turkish population. When no mutations are detected (pathogenic/probably pathogenic) in clinically compatible cases, Multiplex Ligationdependent Probe Amplification analysis contributes significantly to the diagnosis.
囊性纤维化是一种常发生于白种人的常染色体隐性遗传性多系统遗传疾病，也是肺部疾病中最常见的致死和致残原因。目前，已发现超过 2000 种致病基因突变，且这一数字还在随着研究的开展而不断增加。尽管尚无足够包含土耳其人群的数据，但最近研究的增多值得关注。
发现中安纳托利亚地区囊性纤维化患者的基因变异情况。
横断面研究。
本研究于 2014 年 7 月至 2017 年 12 月在土耳其三个儿科肺病学部门（开塞利、科尼亚和安卡拉）的中安纳托利亚地区进行。采用 Sanger 和下一代测序技术对囊性纤维化跨膜电导调节因子（CFTR）基因的外显子和外显子-内含子边界进行分析，对部分患者采用多重连接依赖性探针扩增技术（MLPA）进行大片段缺失和重复的突变分析。
对 316 例患者进行了 CFTR 基因分析，其中 215 例患者被遗传诊断为囊性纤维化。在这些患者中发现了 63 种不同的变异，其中 7 种是通过 MLPA 方法检测到的大片段缺失/重复。最常见的变异是 F508del（29.6%）、G85E（8.2%）、N1303K（8.2%）、Y515*（7.5%）和 G542*（3.4%）。
通过测序和多重连接依赖性探针扩增技术，发现了 7 种以前未在文献中报道的新突变，这有助于更好地了解土耳其人群中 CFTR 突变的异质性。在临床相符的病例中未发现（致病性/可能致病性）突变时，多重连接依赖性探针扩增分析对诊断有重要贡献。
