Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Department for Pulmonary and Auergology, University Children's Hospital, Belgrade, Serbia.
Genet Test Mol Biomarkers. 2020 Apr;24(4):212-216. doi: 10.1089/gtmb.2019.0171.
High heterogeneity levels of cystic fibrosis transmembrane regulator (CFTR) are manifested in different populations. The aim of this study was to analyze comprehensively all mutations in the CFTR gene in Serbian patients with cystic fibrosis (CF) and to use the findings to propose a testing algorithm for the Serbian population. Cascade screening was employed to detect mutations in the CFTR gene of 90 patients suspected of having CF, using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism or PCR-mediated site directed mutagenesis, Sanger sequencing, and/or next-generation sequencing. This is the first report for the Serbian CF population where single nucleotide polymorphisms, small insertions and deletions, large genome rearrangements, and copy number variants were analyzed in detail. A high degree of heterogeneity within the CFTR was documented among our cohort of 90 patients. We identified 19 CF-causing mutations and 3 with varying consequences, including a previously unreported deletion of the entire exon 11. Considering the spectrum and frequency of mutations found, we recommend a multistep sequencing algorithm in combination with evaluation of large rearrangements for future analyses of the CFTR gene in the Serbian population.
囊性纤维化跨膜转导调节因子（CFTR）在不同人群中的异质性水平很高。本研究旨在全面分析塞尔维亚囊性纤维化（CF）患者 CFTR 基因的所有突变，并利用这些发现为塞尔维亚人群提出一种检测算法。 对 90 名疑似 CF 患者的 CFTR 基因进行级联筛查，使用聚合酶链反应（PCR）、PCR-限制性片段长度多态性或 PCR 介导的定点诱变、Sanger 测序和/或下一代测序。 这是首次对塞尔维亚 CF 人群进行报告，其中详细分析了单核苷酸多态性、小插入和缺失、大片段基因组重排和拷贝数变异。我们在 90 名患者的队列中记录了 CFTR 内的高度异质性。我们鉴定了 19 个导致 CF 的突变和 3 个具有不同后果的突变，包括以前未报道的整个外显子 11 缺失。 考虑到发现的突变谱和频率，我们建议在未来对塞尔维亚人群的 CFTR 基因进行分析时，采用多步测序算法结合大片段重排评估。
