Donos Mădălina Andreea, Butnariu Lăcrămioara Ionela, Anton Păduraru Dana Teodora, Murgu Alina Mariela, Rusu Cristina, Pânzaru Monica Cristina, Popescu Roxana, Țarcă Elena, Cojocaru Elena, Ghiga Gabriela, Trandafir Laura Mihaela
Department of Mother and Child, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania.
Department of Medical Genetics, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania.
J Clin Med. 2025 Jul 29;14(15):5362. doi: 10.3390/jcm14155362.
: Cystic fibrosis (CF) is a rare autosomal recessive genetic disease that has a progressive and multisystemic course. The spectrum and frequency of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) vary both in European countries and in other geographical regions. The aim of our retrospective study was to present the genetic variants identified in a group of 48 CF patients from the Moldova region (Romania), as well as to establish genotype-phenotype correlations. : Genetic testing was initially performed for 38 mutations, and in heterozygous patients or those in whom no mutation was detected, gene sequencing (NGS) was performed. : The compound heterozygous genotype was identified in 26 (54.16%) of the patients (with one of the alleles being F508del), while 22 (45.83%) patients had the homozygous F508del genotype. The F508del variant was the most frequent (69.79%), followed by G542X (6.25%, 6/96). Several new variants were also identified that had not been reported in other studies from Romania (R1158X, K598*, R347H, c.2589_2599del, R496H, and CFTRdele2). Phenotypic manifestations in patients with class I, II, III and VII variants (homozygous and compound heterozygous) were more severe compared to those in patients with class IV, V and VI mutations, with the data obtained being consistent with those in the literature. Respiratory tract involvement was present in 77.08% of the patients, being more frequent in patients with the compound heterozygous genotype compared to the homozygous F508del genotype. Most patients had exocrine pancreatic insufficiency (EPI) (85.41%). Gastrointestinal manifestations included hepatocytolysis (66.66%) and biliary cirrhosis (0.41%). Meconium ileus was detected in 18.75% of patients, all with a compound heterozygous genotype. : We compared the results obtained with data from the literature and correlated the detected variant (genotype) with the phenotypic manifestations, highlighting certain particularities present in some patients. Genetic testing allows for early diagnosis and adapted management, including personalized treatment for each patient. Identification of novel unclassified variants still remains a challenge for clinicians. NGS-based screening of heterozygous healthy carriers is important for both genetic counseling and prenatal diagnosis.
囊性纤维化（CF）是一种罕见的常染色体隐性遗传病，病程呈进行性且累及多系统。在欧洲国家和其他地理区域，编码囊性纤维化跨膜传导调节因子（CFTR）的基因突变谱和频率各不相同。我们这项回顾性研究的目的是展示在一组来自摩尔多瓦地区（罗马尼亚）的48例CF患者中鉴定出的基因变异，以及建立基因型与表型的相关性。
最初对38种突变进行了基因检测，对于杂合子患者或未检测到突变的患者，则进行基因测序（NGS）。
26例（54.16%）患者鉴定为复合杂合子基因型（其中一个等位基因为F508del），而22例（45.83%）患者为纯合子F508del基因型。F508del变异最为常见（69.79%），其次是G542X（6.25%，6/96）。还鉴定出了一些罗马尼亚其他研究中未报道的新变异（R1158X、K598*、R347H、c.2589_2599del、R496H和CFTRdele2）。与IV、V和VI类突变患者相比，I、II、III和VII类变异（纯合子和复合杂合子）患者中的表型表现更为严重，所获数据与文献报道一致。77.08%的患者有呼吸道受累，复合杂合子基因型患者比纯合子F508del基因型患者更常见。大多数患者有外分泌胰腺功能不全（EPI）（85.41%）。胃肠道表现包括肝细胞溶解（66.66%）和胆汁性肝硬化（0.41%）。18.75%的患者检测到胎粪性肠梗阻，均为复合杂合子基因型。
我们将所获结果与文献数据进行了比较，并将检测到的变异（基因型）与表型表现相关联，突出了部分患者中存在的某些特殊性。基因检测有助于早期诊断和适当管理，包括为每位患者提供个性化治疗。识别新的未分类变异对临床医生来说仍然是一项挑战。基于NGS筛查杂合子健康携带者对遗传咨询和产前诊断都很重要。
