A Unique Combination of Heterozygous CFTR Gene Variants in a Person with Cystic Fibrosis and Mycobacterium abscessus Infection.

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.

© 2025 S. Karger AG, Basel.