CFTR Haplotype with с.2052-2053INS (2184іnsA) Pathogenic Variant among Patients with Cystic Fibrosis from Ukraine

Abstract Considering the high frequency of 2184insA detected in Western Ukraine in patients with cystic fibrosis, the aim of this study was to conduct a molecular genetic analysis of CF chromosome haplotypes with 2184insA insertion and intragenic microsatellite loci IVS8CA and VS17bTA, to determine the origin of this mutation in Ukraine by comparative analysis with other studies, and to provide updated data on the distribution of CFTR gene mutations in CF patients in Ukraine. The 2184insA insertion was found to be the second most prevalent mutation among cystic fibrosis patients in Ukraine, accounting for 7.3% of mutant alleles of the CFTR gene. At the same time, the highest proportion of chromosomes with this mutation (9.4%) was found in a cohort of patients from the western region of Ukraine. The haplotype analysis using two intragenic microsatellite polymorphisms (IVS8CA and IVS17bTA) on 68 chromosomes with the 2184insA mutation revealed a common origin of this mutation among patients from Ukraine: it was associated with the microsatellite haplotype 16-7/IVS8CA-IVS17bTA. The results support the previous hypothesis that Galicia is the most likely place of origin of the 2184insA mutation and that its high frequency in the western part of Ukraine may be due to the regional founder effect.