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

Arthur Lemson; Cedric Bosteels; Jakko van Ingen; Monique Reijers; Dineke Westra; Wouter Hoefsloot

doi:10.1159/000545552

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

Respiration. 2025 Mar 28:1-5. doi: 10.1159/000545552. Online ahead of print.

Authors

Arthur Lemson¹, Cedric Bosteels^{1

2

3

4}, Jakko van Ingen⁵, Monique Reijers¹, Dineke Westra⁶, Wouter Hoefsloot¹

Affiliations

¹ Department of Pulmonary Diseases, Research Institute for Medical Innovation, Radboud University Medical Center, Radboudumc Community for Infectious Diseases, Nijmegen, The Netherlands.
² Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
³ Respiratory Infection and Defense Lab (RIDL), Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
⁴ European Reference Network on Rare Respiratory Diseases (ERN-LUNG), Frankfurt am Main, Germany.
⁵ Department of Medical Microbiology, Research Institute for Medical Innovation, Radboudumc Community for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
⁶ Department of Human Genetics, Radboud University Medical center, Nijmegen, The Netherlands.

PMID: 40159410
DOI: 10.1159/000545552

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.

Keywords: CFTR modulation therapy; Cystic fibrosis; Mycobacterium abscessus infection; Organoids.

Publication types

Case Reports