Introduction: More than 2000 mutations have been identified since the discovery of the CFTR gene in 1989. However, only 346 mutations have been classified as cystic fibrosis (CF)-causing mutations. Due to the increasing number of mutations and poor correlation between the genotype and phenotype, there is an urgent need to determine the mutations that are pathogenic, nonpathogenic, or lead to variable symptoms.
Aim: The aim of the study was to present the clinical characteristics of Polish patients with rare and novel CFTR mutations, with an attempt to determine the pathogenicity status of those variants.
Materials and methods: The group included 13 patients born between September 2006 and May 2019, who underwent CF newborn screening and in whom two CFTR mutations, including at least one rare or a novel mutation, were identified.
Results: We identified 13 patients with mutations in both alleles of the CFTR gene, one of which was at least rare in Polish population (R289NfsX17, I618RfsX2, T682KfsX40, S1347PfsX13, W356X, E33X, dup.16,17A) or was a mutation of unknown clinical consequences (H199R, L468P, A1217E, Q359R, T1036I, W1282R). None of them were described in the CFTR2 database. In all examined patients, sweat tests were elevated. The diagnosed patients presented with a wide spectrum of clinical symptoms. Broad clinical characteristics and test results are presented.
Conclusion: Pathogenic mutations are H199R, L468P, A1217E, Q359R, T1036I, W1282R, R289NfsX17, I618RfsX2, T682KfsX40, S1347PfsX13, W356X, E33X, dup.16,17A. Every patient with a mutation of unknown clinical consequences in one CFTR allele requires attentive follow-up.
Keywords: CFTR; clinical manifestation; cystic fibrosis; newborn screening; pancreatic insufficiency; pancreatitis; rare mutations; sweat chloride.
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