Abstract
Introduction: Cystic fibrosis (CF) is a genetic disorder caused by mutations in the CFTR gene. A minority of people with CF carry two heterozygous CFTR mutations other than the common Phe508del, complicating diagnosis and treatment. Case Presentation: We report the case of a 25-year-old South American male diagnosed with CF respiratory disease, characterized by a history of recurrent infections, pulmonary Mycobacterium abscessus infection, airway disease on high-resolution CT, and an elevated sweat chloride level (74 mmol/L). Exome sequencing identified a unique combination of CFTR mutations: a pathogenic frameshift variant (c.2052dup) and a variant of unknown clinical significance (c.710A>C). Notably, there were no signs of pancreatic insufficiency. Rectal mucosal organoid cultures demonstrated residual CFTR function with responsiveness to ivacaftor and the combination of elexacaftor, tezacaftor, and ivacaftor. Conclusion: This case highlights a unique combination of heterozygous CFTR variants in a person with CF respiratory disease, which may be amendable to CFTR modulation therapy.
